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COMMUNICATIONS TO THE EDITOR
limit; while the other phase (p) is present alone wherever this limit is exceeded. They also make plain the migration of the phase boundary with continued diffusion. Finally they show that the higher order diffraction lines from the 0 phase are much less intense than those of the a phase, a
Vol. 62
fact probably due to the severe cold working which occurs as j3 is formed from CY by a sudden expansion of Over 3% (linear) a t the advancing Phase
~ ~ ~ ~ ~ , s I PITTSBURGH, PENNSYLVANIA
RECEIVED JUNE 8,1940
COMMUNICATIONS T O T H E EDITOR or 2,3 for the ring double bond in cannabidiol or in the tetrahydrocannabinols are thus excluded. The migration of the double bond in the tetrahydrocannabinol, if 2,3 or 5,6, should proceed to Sir: the most favored position, in conjugation with Certain mild reagents (previous papers V, VI) the benzene ring. As this does not occur, posiconvert cannabidiol into a tetrahydrocannabinol tions 3,4 and 4,5 remain and are considered the [a]3 2 ~ 165 * 7'; more vigorous reagents to one most probable The 3,4 is assigned to the lowerwith [ a ] 3-240 2 ~ =t10". It is obvious from the rotating tetrahydrocannabinol (I) and the 4,5 to rotations that these forms are not absolutely pure the higher-rotating (11), for migration from the and each is probably contaminated with the other. 3,4 to the 4,5 position (which has the methyl The lower-rotating tetrahydrocannabinol can substitution) is more likely than Wice versa. be converted to the higher-rotating by the same Through its relationship to the lower-rotating reagents and under the same conditions which tetrahydrocannabinol, cannabidiol may be postuconvert cannabidiol to the higher-rotating form ; lated as having structure 111. thus the lower-rotating form is presumably the CHB initial reaction product in the isomerization of cannabidiol and the higher-rotating form a secondary product. Therefore, the lower-rotating form probably has the double bond in the same /\ position as the corresponding double bond in CHa CHs cannabidiol. Cannabidiol has been shown to have no double bond conjugated to the benzene ring; that its two double bonds are not conjugated to each other is indicated by the very close values of the absorption spectrum of cannabidiol (maximum /\ CHa CHa log E , 3.18), and that of tetrahydrocannabidiol I1 (3.05) and confirmed experimentally by failure of repeated attempts to condense cannabidiol dimethyl ether with maleic anhydride. The double bond in each of the tetrahydrocannabinols has been shown not to be conjugated to the aromatic /\ CHa CHI nucleus by comparison of their physical constants I11 with that of a synthetic tetrahydrocannabinol of The tetrahydrocannabinols have a very potent unequivocal constitution with the double bond conjugated (see paper VII). Positions 1,2 or 1,6 marihuana activity which is markedly greater STRUCTURE OF CANNABIDIOL. VIII. POSITION OF THE DOUBLE BONDS IN CANNABIDIOL. MARIHUANA ACTIVITY OF TETRAHYDROCANNABINOLS
COMMUNICATIONS TO THE EDITOR
Sept., 1940
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methyl, due t o the large. number of electrons. Conclusion of complete calorimetric measurements in this Laboratory down to 12'K. on silicon tetramethyl permits a n accurate estimate of the hindering potential. The entropy has been calculated using the following frequencies and distances':
than that of the synthetic optically inactive form with the double bond conjugated to the benzene ring. The hexahydrocannabinols have less marihuana activity. Comparative pharmacological values with that of a highly potent product obtained by Dr. J. C. Matchett through fractionation of purified red oil in a molecular still and used as a standard by Dr. S. h e w e a t the Cornell Medical School in tests according to his procedure of "Bioassay by Approximation" ( J . Am. Pharm. Assoc., 28, 427 (1939); J . Phurm. Exptl. Therap., 66,23 (1939)) are shown in Table I.
Carbon skeleton: IwI = 598, 2w2 = 202, 3 w 4 , ~ , = ~ 239, = 800 cm.-l. CHa internal: '6(a) = 1264, Q(u) = 1427, I P ( T ) = 2905, %(u) = 2963 em.-'. CHa rocking: = 950 cm.-l. Distances: Si-C = 1.93 A,, C-H = 1.09 A. 307,8,9
The frequency 3w7,~,9 is estimated from the frequencies 696 and 831 ern.-' which are apMean value parently a result of resonance degeneracy. The potency max. deviation rocking frequencies are estimated by analogy 1.00 with ethane. The calculation of the entropy a t 0.00 227.00'K. and at 299.8'K. (the normal boiling 2.15 * 0.66 1.75 * .25 point) is summarized in Table I along with the 0.70 * .,lo corresponding calorimetric values.
TABLE I BIOASSAY O F TETRAHYDRO AND HEXAHYDRO CANNABINOLS Substance
Min. Max. Potency above below
Standard red oil ........ ........ Cannabidiol Tetrahydrocannabinol, - 165O 1.50 2.80 Tetrahydrocannabinol, -240" 1.60 2.00 Hexahydrocannabinol, -70" 0.60 0.80 Tetrahydrocannabinol (syn.) .13 .27 .10 .20 Hexahydrocannabinol (syn.)
.20 * .07 .15 * .05
The acetates and methyl ethers of the two tetrahydrocannabinols were colorless, highly viscous oils. Tetrahydrocannabinol [a]a 4 ~- 164' gave an acetate [ a ] " ~-167' and methyl ether [a]a 2 ~ - 166'; tetrahydrocannabinol [a]3 0 -2240' gave an acetate [a]a 4 -229' ~ and methyl ether [ a I 3 * D -226'. NOYESCHEMICAL LABORATORY UNIVERSITY OF ILLINOIS ILLINOIS URBANA, INCOLLABORATION WITH TEIE TREASURY DEPARTMENT NARCOTICS LABORATORY D. C. WASHINGTON, RECEIVED AUGUST13, 1940
TABLE I THE ENTROPYOF SILICONTETRAMETHYL IN THE IDEAL GAS STATE FROM MOLECULAR AND SPECTROSCOPIC DATA 227.0°K., e. u.
~
Translational and rotational (free) 72.40 Vibrational ( 3 0 7 , ~ , 9 ) 0.23 Vibrational (8S = 950) .28 7.59 Vibrational (other modes)
Total ROGERADAMS Calorimetric S. LOEWE (Sr - S) X 4 (experiD. C. PEASE e. K. CAIN mental) R. B. WEARN (S - S) X 4 (V = 1280, R . B. BAKER I = 5 . 3 x 10-40) HANSWOLFF
HINDERED INTERNAL ROTATION OF METHYL GROUPS: THE ENTROPY OF SILICON TETRAMETHYL
Sir : We have recently completed an investigation which indicates that the potential hindering internal rotation of methyl groups is probably due to hydrogen repulsions. A study of the entropy of gaseous silicon tetramethyl yields a potential of 1280 calories, compared to 4800 calories for tetramethylmethane. If the potential were mainly due t o lack of cylindrical symmetry in the bond orbitals caused by electron interactions, a higher potential than 4800 calories might be predicted for silicon-tetra-
80.50 77.94 2.56 2.56
* 0.08 *
.OS
299.S°K., e. 11.
75.73 0.64
=t0.1 .S5 * .2
10.59
* 0.16 .30
87.81 86.33
* 0.46
1.48
*
+
*
0.3 .6
* 0.9
1.73
The heat of vaporization was obtained temporarily from the measured vapor pressure equation and approximate state data. Hence the larger error a t the higher temperature where the correction to the gas volume is larger. The potential of 1280 =t 160 calories was obtained from Pitzer's tables2 to fit the experimental discrepancy, (S, - S) X 4. At the lower temperature if the 950 frequency were in error by 200 cm.-', and if w7,8,9 should really be a t 696 em.-', the entropy would only be raised by 0.7 e. u. and the potential would then be 1600 calories. THESCHOOL OF CHEMISTRY AND PHYSICS THEPENNSYLVANIA STATE COLLEGE J. G. ASTON STATE COLLEGE, PA. R. M. KENNEDY RECEIVED AUGUST23, 1940 (1) Rank and Bordner, J . Chcm. Phys., 3, 248 (1935). (2) Pitzer, ibid., 6, 469 (1937).
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COMMUNICATIONS TO THE EDITOR
Vol. 62
THE SYNTHESIS OF I-beta-GLUCOSIDOFRUCTOSE. A CORRECTION
orcinol and olivetol in the presence of sulfuric acid have been carried out with subsequent treatment Sir * with methylmagnesium iodide to give the tetraI n a recent publication by Pacsu, Wilson an1 hydropyran I (plates from alcohol, m. p. BSo, Graf [THISJOURNAL, 61, 2675 (1939)l 1-8-gluco- found: C, 84.24; H, 8.98; calcd.: C, 84.2; sidofructose was described as a new disaccharide. H, 8.77) and the g‘ycol I11 (white crystals, m. p. The authors regret that in carrying out and pub- 105-106°, found: C, 74.47; H, 8.98; calcd.: C, lishing their work they have overlooked the fact 74.5; H, 8.98). that the same sugar had previously been preCHs CHa / / pared by Brigl and Widmaier [Bar., 69, 1210 (1936)] by a different method. The latter investigators used dibenzal-iructopyranose as start/-\/-\ing material and obtained the disaccharide in a CHI CHa CHI CHs 18.8% over-all yield, whereas Pacsu, Wilson and Graf prepared the sugar from 2,3-4,5-diacetoneP-fructopyranose in a 50% yield. The physical constants of the disaccharide as reported from the two sources are practically identical. It should be added that no reference to the work of Brigl and Widmaier can be found either in the latest book on the carbohydrates (Micheel, “Chemie der Zucker und Polysaccharide,” Akademische Verlagsgesellschaft m. b. H., Leipzig, 1939), or in the latest comprehensive report on the syn/\ thesis of the oligosaccharides (ZemplCn, “Neuere CHa CHs Richtungen der Oligosaccharid-Synthese” in IV “Fortschritte der Chemie organischer NaturOH stoffe” edited by Zechmeister, Julius Springer, CHa a \ -> - O C s H l l ( n ) Wien, 1939).
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