1190
Vol. 77
ALEXNICKON
Further elution of the column with methanol gave 65 mg. Anal. Calcd. for CZZHZ~ON: C, 82.20; H , 8.47; N, 4.36. of yellow gum which was not investigated further. Found: C, 82.09; H , 8.31; N, 4.50. In another experiment, in which the temperature was 6-Carboxyamido[4.4]paracyclophane.-A mixture of 305 allowed t o rise to 50', a white solid was isolated in approxi- mg. (0.001 mole) of acid VI and 1.5 ml. of thionyl chloride mately 35% yield. This is probably l-keto-cis-5,6,7,8,9,10- was heated on the steam-bath for 30 minutes, the excesq hexahydro[4.4]paracyclophane, arising from oxidation of thionyl chloride then being removed under vacuum. The the benzyl position. One crystallization from methanol residue, on treatment with cold concentrated ammonia, Amin. 225 rnp (e, 2,100), gave needles, m.p. 73.5-74.5'; gave a viscous oil which slowly solidified. One crystallizaAmax. 253 mp (e, 12,100),hahoulder 305 m r (e, 300).14 tion of the compound from aqueous ethanol and recrystalAnal. Calcd. for C2oHz8O: C, 84.45; H, 9.92. Found: lization from cyclohexane gav; 177 mg. (57.5%) of the amide of acid VI, m.p. 180-182 C, 84.25; H, 9.74. 16-Amiio-cis-5,6,7,8,9,l0-hexahydro [4.4]paracyclophane. Anal. Calcd. for Cz1Hz60N: N, 4.56. Found: N, 4.34 -A solution of nitro compound VI11 (0.304 g., 0.000965 Rearrangement of the Preceding Amide to 6-Acetamidomole) in 95% ethanol (20 ml.) was shaken in hydrogen in [4.4]paracyclophane (VII).-To a solution prepared from the presence of 50 mg. of platinum oxide until absorption of 14 mg. (0.6 mmole) of sodium and 0.4 ml. of methanol was hydrogen ceased (73.7ml. a t 22" (748mm.), 103%). The added 92 mg. (0.3 mmole) of the preceding amide, followed catalyst and solvent were removed, the residue was dissolved by 48 mg. (0.3 mmole) of bromine, the resulting mixture in ether, and the solution was washed with water and dried. being heated on the steam-bath for 10 minutes. The solRemoval of the ether gave 274 mg. (99%) of the amine, vent was then removed under reduced pressure, and the b.p. 200" (bath temp.) (0.1 mm.). residue was taken up in ether. The solution was washed Anal. Calcd. for C Z O H ~ LC, N :84.15; H, 10.95; N, 4.91. with water, dried and evaporated to give an oil which partially solidified. This material was heated under reflux for Found: C, 84.36; H , 10.97; N, 4.98. 16-Acetamido-cis-5,6,7,8,9,10[4.4]paracyclophane (X).- 6 hours with 0.12 g. of potassium hydroxide in aqueous The above amine (175 mg.) was heated under reflux for 25 methanol in order to hydrolyze any unreacted starting mateminutes with 1 ml. of acetic anhydride, and the mixture rial. The basic solution was diluted with water and eswas diluted with water. The resulting soapy solid was tracted with ether. Removal of the ether gave an oil which taken up in ethanol water (3:1) and filtered to give 141 mg. was heated under reflux for 1 hour with 0.3 ml. of acetic (70%) of crude amide, m.p. 184-186'. One crystallization anhydride and 0.4 mI. of pyridine. This solution was diluted with water and extracted with ether. The ethereal from ethanol gave 119 mg. (needles) of X, m.p. 186-187'; extract was washed with dilute acid and dilute base, dried; hshouldsr 234 mP (e 7,350),Xshoulder 273 mp (e 885). evaporated. The residual solid on sublimation (140 Anal. Calcd. for C Z Z H ~ ~ O N C,: 80.68; H , 10.16. and (0.0,6 mm.)) gave 35 mg. (36%) of amide VII, m.p. 172Found: C, 80.84; H , 10.02. 174 , undepressed upon admixture with the authentic 6-Acetamido[4.4]paracyclophane (VII).-Acetamido specimen described above. compound X (172 mg.) was dehydrogenated with 35 mg. of Schmidt Reaction with 6-Acetyl[4.4]paracyclophane (111). 10% palladium-on-charcoal by heating a t 280-300' until -Ketone I11 (0.708 g., 2.31 mmoles) was added to 7 g. of the evolution of hydrogen ceased. During this operation, a trichloroacetic acid and 0.68 g. of concentrated sulfuric large amount of solid sublimed into the neck of the flask, acid, the resulting mixture being maintained a t approxithus making it impossible to ensure complete dehydrogena- mately 60" while 0.265 g. (4.1 mmoles) of sodium azide was tion. The product was then taken up in ethyl acetate and added over a period of 25 minutes. After 90 minutes, the filtered. Removal of the ethyl acetate gave a solid which mixture was cooled, diluted with water and extracted with was crystallized once from aqueous methanol and once from ether. The ethereal solution was washed with water and cyclohexane to yield 73 mg. (43%) of the aromatic amide dilute base and dried. Removal of the ether gave 618 mg. VII, m.p. 172-174'. The compound sublimed a t 138' (0.05 of solid which was crystallized from 12 ml. of cyclohexanemm.) to yield prisms, m.p. 173-174.5': hahoulder 233 mp (e, benzene (3:l)to yield 513 mg. (69%) of the amide VII, m.p. 5,660), himeotion273 mp (e, 9971,Am=. 274 m p (e, 1,050). 170-171.5', undepressed upon admixture with the authentic specimen described above. (14) Compare the spectrum of this compound with t h a t of l-ketoLos ASGELES,CALIFORNIA 7,8,9,10,1l,l2-hexahydro[6.6]paracyclophane (ref. 2.)
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[CONTRIBUTION FROM THE DEPARTMENT O F CHEMISTRY O F BIRKBECK COLLEGE]
The Structure of the Caryophyllene-Maleic Anhydride "Adduct" BY ALEXKICKON' RECEIVED AUGUST 9, 1954 The compound formed on combination of caryophyllene and maleic anhydride is shown t o have the structure S I . Formulas for derived rearrangement products are proposed.
In 1935 Ruzicka and Zimmermann2 reported that treatment of caryophyllene (CISH24) with maleic anhydride in hot benzene solution produced a crystalline (m.p. 98')) 1 : l addition product. Even though the constitution of caryophyllene itself was unknown at that time, their findings became of considerable interest when subsequent work revealed that the two double bonds in the original hydrocarbon were not ~ o n j u g a t e d . ~Furthermore, (1) National Research Council of Canada Postdoctorate Fellow; present address, National Research Council of Canada, Ottawa 2, Ontario. (2) L. Ruzicka and W. Zimmermann, Helv. Chin. Acta, 18, 219 (1935). (3) (a) N. F. Goodway and T. F. West, J . Chem. S o c . , 1853 (1939); (b) Y.R. Naves and E. Perrottet, Hclu. Chin. Acta, 24, 789 (1941).
the catalytic hydrogenation experiments of R u zicka, Plattner and Balla4 later revealed that the maleic anhydride addition product still retained two double bonds, and so indicated that this "adduct" was not one of the usual Diels-Alder type. The nature of this unusual reaction became more understandable through an important fundamental discovery by Alder, Pascher and Schmitz in 1943.5 These investigators found that many mono-unsaturated olefins combined with maleic anhydride at elevated temperatures (ca. 200') to form products in which the anhydride residue was attached to the saturated carbon of an allylic system. The adjoin(4) L Ruzicka, P A Plattner and G Balla, tbtd , 24, 1219 (1941) ( 5 ) K. Alder, F Paschcr and A Schmitz, BLY, 76B,27 (1943)
March 5, 1955
STRUCTURE OF THE CARYOPHYLLENE-MALEIC ANHYDRIDE ADDUCT
1191
oxane-hydrochloric acid. Saponification of this substance gave the corresponding hydroxy-dibasic acid, from which the original lactonic acid was regenerated when melted. CHzxCHCHa HC-C Benzene II 0 We believed that useful structural information HC-C 12 hr., 250” could be obtained through additional investigation L O 0 of such cyclization products, particularly in view of the wealth of knowledge on the rearrangements of CH~=CHCH~-CH-C~ I \o caryophyllenic systems recently made available by the researches of Barton and his colleague^.^^'^ The infrared absorption curve ((2%)of the lacdride “adduct” is derived by some such allylic tonic acid (m.p. 208’) exhibits bands a t 1712 and process has since been generally al- 1734 cm.-’. The former peak is attributed to the though no structures have been proposed.s carboxyl group, and the latter one to the ester linkThe objective of this paper is to adduce evidence age of a &lactone system.15 The spectrum of the for the constitution of the “adduct” in the light of derived methyl ester (CCL) shows only one carthe recently established9 structure for caryophyl- bonyl band in the infrared (1742 cm.-’), of double lene (IlO). An important feature of the unique skele- the usual intensity. ton in the sesquiterpene is the presence of a transA substance with probably the same tricyclic oriented, endocyclic double bond. That this ar- skeleton is obtained by the action of dry hydrogen 2 3 chloride on a cold, chloroform solution of the “ad-duct.” Under these conditions one molecule of hydrogen chloride is incorporated to yield a compound (see partial structure VI) that is saturated to tetranitromethane and that has the anhydride lo 7 //I I1 ring intact. This finding confirms the recent report that a monohydrochloride was formed on treatment --d-\C02H of the “adduct” with ethereal, dry hydrogen chloride, but contradicts the suggestion that this hydrokCO*H I11 chloride has resulted from simple addition to one of the olefinic linkages.16 The chloro compound on rangement imparts steric strain to the system is acid hydrolysis is transformed to the same &lacclear from the observation that caryophyllene can tonic acid (VII) described above. That the anhydride residue and the hydroxyl be isomerized with nitrous acid to isocaxyophyllene (11), which has the same endocyclic link in the group involved in lactonization are attached to a more stable, cis configurati~n.~The relevance of pair of contiguous carbon atoms is clear from the following observations. Under the influence of Nthese points is considered in the sequel. Degradation of the “adduct” by oxidation has bromosuccinimide in aqueous dioxane the “adduct” been attempted by Ruzicka, Plattner and Werner.“ takes on the elements of HOBr and yields two isoWith the use of ozone followed by potassium per- meric products. One of these is a bromoalcohol manganate at room temperature they obtained with the anhydride ring intact (IV). The other subhomocaryophyllenic acid, a substance now known to stance is a bromo-y-lactonic acid (V) as evidenced possess structure III.12 Two conclusions concern- by the infrared absorption of the derived methyl esing the “adduct” can be drawn from these results. ter (1740 cm.-’ COOCHz; 1775 cm.-’ y-lactone). Firstly, the four-membered ring remains intact ; Both products are saturated and therefore tricyclic. secondly, there is no unsaturation a t the centers On very mild, acid-catalyzed hydration the bromoalcohol IV isomerizes to the bromo-y-lacC-9, C-1, C-2 or C-3 (see I for numbering system). Of the several transformations recorded by Ru- tonic acid (V) in 50% yield,“ whereas on stronger zicka, Plattner and Balla4 for the “adduct,” the acid hydrolysis both substances IV and V generate ready conversion to a saturated, tricyclic13 lactonic an isomeric bromo-&lactonic acid (infrared spectra acid (m.p. 208O) appears germane. This hydration- of methyl ester in CCL, 1744 em.-’ double normal cyclization was originally conducted in aqueous intensity), represented by the part-structure VIII. acid or boiling water, but proceeds better in hot, di- Removal of the bromine from VI11 with zinc dust or by catalytic hydrogenolysis proceeds smoothly (6) P. A. Plattner and L. Werner, Hclu. Chim. A c f a , 27, 1010 (1944). (7) J. L. Simonsen and D . H. R. Barton, “The Terpenes,” Vol. 111, and yields the original &lactonic acid (VII) obtained by Ruzicka, Plattner and Balla. The University Press, Cambridge, Eng., 1952, p. 69. ( 8 ) For a discussion see, Ann. Rep., 44, 157 (1947). The simplest explanation of these facts is that (9) For pertinent data and leading references, see A. Aebi, D. H. R. all the tricyclic compounds formulated partially Barton and A. S. Lindsey, J . Chem. Soc., 3124 (1953). A review OS the in the accompanying reaction scheme possess an recent developments in caryophyllene chemistry is also available [A.
ing scheme illustrates the reaction for the case of propylene. That the caryophyllene-maleic anhy-
+
P-
+,-J+ I-[-y a*
Nickon, Perjumery Essoit. Oil Record, 46, 149 (1954)l. (lo) A heavy dot represents the projection of a hydrogen atom above the plane of the molecule; an open circle denotes a center of unknown stereochemistry. (11) L. Ruzicka, P. A. Plattner and L. Werner, Helv. Chim. Acta, ’36, 966 (1943). (12) T . L. Dawson and G. R. Ramage, J . Chcm. Soc., 3382 (1951). (13) This terminology refers to carbocyclic rings only and does not include lactone or anhydride systems.
( 1 4 ) (a) D. H. R. Barton, T. Bruun and A. S. Lindsey, J . Chem. Soc., 2210( 1952); (b) A. Aebi, D. H. R. Barton, A. Burgstahler and A. S.
Lindsey, ibid.. in press. (15) Although the infrared evidence does not exclude lactonic rings of size greater than six atoms, their presence is substantially precluded by the ease of reclosure of the lactone system. (16) G. S. Krishna Rao. S. Dev and P. C. Guha, J . Indian Chcm. SOL, ae, 598 (1952); c. A , , 47,8697 (1953). (17) The remainder is recovered starting material.
1192
.\LEX
NICKON
VOl. 77 3 rings
2 double bonds C-OH mild
CHZ-C
