6280
STANLEY M. BLOOM
Vol. 80
3-(o1-Carbamylisopropyl)-5,5-dimethylhydantoin.-The compound IVa (0.7 g., 0.0036 mole) in water (50 ml.) was heated under reflux for 8 hours. The water was removed in ZJUCUO and t h e residue was extracted with acetone (20
acidified with glacial acetic acid and cooled. The precipitated solid (sublimes 280') was recovered by filtration, yield 7.2 g. (68%). The infrared spectrum of this preparation was identical with the spectrum of a known commercial m1.1. The acetone solution was evaporated and the residue sample of a-amiiioisobutyric acid. was crystallized from ethyl acetate, yield 0.22 g. (28.670). Anhydride of 3-a-Carboxyisopropyl-5,5-dimethylhydanThe melting point was raised from 208-216" with dec. to toin.-Benzoyl chloride (0.65 g., 0.0046 mole) was added 216-217' with dec. by further crystallizations from ethyl dropwise to a cooled solution of 3-a-carboxyisopropy1-5,5acetate. dimethylhydantoin and the solution was heated under reAnal. Calcd. for CQHI6N303: 50.70; H , 7.09; K, flux for 25 minutes. The reaction mixture was poured onto crushed ice and the precipitated product (m.p. 204-230') 19.71. Found: C, 50.11; H, 7.07; N,19.81. Method B. 3-(~t-Carbamylisopropyl)-4-imino-5,5-di-was recovered by filtration, yield 0.51 g. (54Gi). Three from absolute methanol (25 ml.) raised t h r methyl-2-imidazolidone Picrate .--A saturated solution (50 crystallizations melting point t o 241-243'. tnl.) of picric acid was added to a solution of IVa (0.29 g., 0.00149 mole) in water (50 ml.) and the mixture was heated Anal. Calcd. for CI8H26N407: C , 52.68; I%, 6.3); S, a t 95' for 20 minutes. The clear solution on cooling de- 13.65. Found: C , 52.31; H, 6.48; SI, 13.21. posited a crystalline picrate (m.p. 238-240"), yield 0.57 g. Nitration of 2-Imin0-3,3,7,7-tetramethyl-5-0~0-2,3,5,6(87.270). Two crystallizations from water raised the melttetrahydro-7(H)-imidaz [3,4-a]imidazole.-2-Imino -3,s,7,7ing point t o 242-242.5'. tetramethyl - 5 -oxo -2,3,5,6 - tetrahydro -7( H)-imidaz [3,4-3]A n d . Calcd. for CijH19K70~: C, 40.81; H, 3.34; N, imidazole (3 g., 0.016 mole) was added over a period of 10 22.22. Found: C, 40.93; H, 4.78; N, 21.78. minutes to a stirred nitration mixture of ammonium chluMethod C. 3-(a-Carbamylisopropyl)-4-imino-5,5-di- ride (1.98 g., 0.037 mole), nitric acid (10.5 g;, 0.15 mole) methyl-2-imidazolidone Hydrochloride.-2-Imino-3,3,7,7- and acetic anhydride (15.3 g., 0.15 mole) a t 0 . The solutetramethyl-5-oxo-2,3,5,6 - tetrahydro-7(H)-imidaz[3,4-a]tlon was alloiyed to \Tarm up t o 27' and the stirring was imidazole (2 g., 0.01 mole) was dissolved in 0.26 >lrethanolic continued for 3 hours. This reaction mixture was poured hydrogen chloride solution ( 6 ml.). The solution was onto ice (250 g.) and the insoluble precipitate (n1.p. 202evaporated t o dryness in Z'UCZLO a t room temperature after 207" dec.) was removed by filtration, yield 3.3 g. ( 7 7 . 3 % ) . which the residual oil crystallized on standing, yield 2.42 g. Four crystallizations from acetone-petroleum ether solutioii (100%). Three crystallizations from methanol-ether solu- raised the melting point t o 214-215' dec. tion raised the melting point from 249-250 to 253 O . .4?tnZ. Calccl. for CgH12Ns05: C, 3S.03; I-I, 4.26; S , A?zal. Calcd. for CQHi?ClhTa02: C, 43.47; H, 6.89; 29.57. Found: C, 38.46; H, 4.61; h-,29.30. C1, 14.26; N, 22.53. Found: C, 43.22; H, 6.86; C1, 2-Sitriniino-2 ,i-ditnethy1-3,7-dietliyl-5-o~o-G-iii~r~-2,:~ ,14.69; N, 22.49. (m.p. 99-102') A sample of the hydrochloride on treatment with aqueous 5,6-tetrahydro-7(H)-imidaz[3,4-a]imidazole was prepared in 69.5y0 yield under similar conditions. picric acid solution gave a picrate melting a t 239-240", Several crystallizations from acetone-petroleum ether soluyield 89%. A mixture melting point determination with the picrate (m.p. 242-242.5') prepared by method B gave tion raised the melting point t o 164-165' dec. A n d . C:tlcd. for C11H1~K60,:C, 42.:{1; 1 1 , .7.17: S J no depression. Method D. 3-(a-Carboxyisopropyl)-5,5-dimethylhydan- 26.92. Founti: C , 42.64; H, 5.21; S , 27.32. toin.--A solution of I V a (3 g., 0.0155 mole) in 3 N hydroReaction of a-Aminoisobutyronitrile with Phosgene.--chloric acid solution (100 ml.) was heated a t 80" for 10 IVhen phosgene was passed into a toluene solution of aminutes. The solution was evaporated t o dryness and the nminoisobutyroriitrile following the method of Jacobson4 :L residue was extracted with water. The water-insoluble quantitative yield of crude product melting :it 170-210' de?. residue melted at 208-212', yield 2.40 g. (72.27,). One was obtained. Repeated crystallizations from methanol crystallization from water raised the melting point of the 3- raised the melting point to 240' dec. This product did not depress the melting point of a known sample of 2-imino(a-carboxyisopropyl)-5,5-dimethylhydantoin t o 215-216'. - tetrahydro - 7(H)-imidazAnal. Calcd. for C9HlaN20a: C, 50.47; H, 6.58; Tu', 3,3,7,7-tetrametliyl-5-oxo-2,3,5,6 [3,4-a] imidazole (m.p. 240' dec.) which was prepared a s 13.08; neut. equiv., 214.22. Found: C, 50.2.7; H, 6.06; described above by heating 1,3-di-(cu-c?:Liioisoprop~l)-urea N,13.19; neut. equiv., 214.5. in ethariol under reflux for srreral hours. Method E. a-Aminoisobutyric Acid.-A solution of II'a Acknowledgment.--The infrared absorptioii (20 g., 0.13 mole) and barium hydroxide (19.5 9.) in water (300 ml.) was refluxed for 14 hours. The cooled solution spectra were deteriniried by Dr. C. Sandorfy of the \vas filtered and the precipitate washed with water. After University of Moritrcnl, Montreal, Quebec. the filtrate with washings TWS evaporated to dryness the rcsidue was dissolved in water (30 ml.). This solution was VILLE LASALI.E:. (J!II&;HEC, CASAD.~
c,
[CONTRIHUlION F K O M
THE
CHEMIC-4L
LAIIORATOKI OF SMITH C U I I 1 L L ]
8,lO-Dimethy1-2-ket0-A'~~~~~ '-hexahydronaphthalene : The Dienone-Phenol
Rearrangement BY STANLEY 11.BLOOM RECEIVED MAY29, 1958 The synthesis of 8,10-dimethyl-2-ket0-~'~~~~~~-hexahydronaphthalene (IX) is reported. The phenol, 4,8-diinethyl-6hydroxy-1,2,3,4-tetrahydronaphthalene(XII), obtained on dienone-phenol rearrangement of 1 I X I demonstrates the intermediacy of the spiran intermediate ( X i in the reaction studied.
Woodward and Singh' first demonstrated that the acid-catalyzed rearrangement of cyclohexadienones does not always follow the course of santonin (I) in its conversion to desmotroposantonin (II).2 ( 1 ) K B T\-oodward aud T Singh, HIS J O U R ~ A L ,72, U l (19.50) (2) Hudng Minlon, C Lo and L J Chu, tbrd , 66, 1780 (1943)
10-Methyl-2-keto-A -1,9'3,4-hexahydronaphthalene (111) was synthesized and rearranged in acetic anhydride to 5-hydroxy-S-methyl-l,2,3,4-tetrahydronaphthalene (IV). Extending these data, Woodward and Singh suggested the structure VTa rather than VI1 for the phenol obtained frotii the acid-catalyzed rearrangement of steroid die-
8,1 0 - D ~ E T H Y L - 2 - ~ T O - A 1 8’4-HEXAHYDRONAPHTHALENE ”’
Dec. 5, 1958
qQJo..&
0
I
I1
compound was accordingly synthesized (vide infra)
,”;i3
HO IV
I11
nones of the type V. Inhoffen, et al.,3 earlier had postulated VI1 t o agree with the result of the santonin rearrangement. T o arrive a t VIa the authors proposed a mechanism for the conversion proceeding through the hypothetical intermediate
&@
o
/
Q
0
0
@
0
6281
/
IX
As this cyclohexadienone IX is ideally suited to provide a demonstration of the existence of a spiran intermediate X analogous to VI11 in the dienone-phenol rearrangement, its rearrangement was studied. The phenol XI1 would result if path A (Fig. 1) is followed, while in contrast, path B proceeding through X I would result in the phenol XIII.77s
Jq$Q;wq-@-@ a ;q Path A
10 H
X
0
V
H
KO
HO
XI1
Path B
HO VIb
VI1
VIII. A 1,Sshift of the more highly substituted carbon atom in VI11 led to the product VIa R
cp I
HO
-$Q
to
HO
=
H
XI
@-icj.c’
HO
HO
XI11 Fig. 1.
VI11
rather than VIb obtainable through the migration of the least substituted carbon atoma4 Woodward, et al.,6 in a latter paper, proved the validity of the new assignment. I n the course of other work under way in this Laboratory, we had need of 8,10-dimethyl-2ket~-A~~~;~~~-hexahydronaphthalene (IX),6 and the (3) H. H. Inhoffen and G. Zuhladorff, Be?., 74, 604, 1911 (1941). (4) Two mechanisms were originally considered by Woodward and Singh’ to account for the rearrangement of 111 to IV. T h e possibility that i t is first formed from 111 and then closed to IV by internal electrophilic substitution a t the unblocked o-position was eliminated
&
HO
i on the basis of later work. See R. B. Woodward, “Perspectives in Organic Chemistry,” Interscience Publishers, Inc., New York, N. Y., 1956, p. 178,for the data providing proof of the existence of a spiran intermediate in a case studied, (5) R. B. Woodward, H. H. Inhoffen, H.0. Larson and K. Menzel, B e y . , 86, 594 (1953). (6) T h e compound IX on irradiation with ultraviolet light is expected to give ii, an intermediate in a projected synthesis of vetivone (iii). This work is presently in progress in this Laboratory (see D.
H. R. Barton, P. de Mayo and hl. Shafiq, J. Ciieni. Soc., 939 (1957), for an analogy).
ii
iii
I
(7) A simple 1,Z-methyl shift which was found in the santonin rearrangement but excluded for the steroid dienones on the basis of Woodward’s work, would lead to iv. I
HO iv (8) The dienone v would not allow a choice between path A and B for both pathways would give the pheaol XII. The compound v i s the prototype for the steroid dienones which are not suited for the test
Po V
provided by the present work. In path A, the spiran X is opened in the manner found in the steroid dienone rearrangement, ;.e.. the more highly substituted carbon atom migrates preferentially ( v i d e supra).
STANLEY M. BLOOM
6282
Vul.
so
Rearrangement of I X in acetic anhydride t o character, being insoluble in 5yosodium hydroxide which a trace of sulfuric acid had been added solution bide inj~u)led to the isolation of the phenol XII. Experimental Partl5 This finding is in accord with the work of Woodward 8,l0-Dimethyl-2-keto-A1~9~~~~-hexahydronaph~a1ene.and Singh1f4and reaffirms the intermediacy of the 2-Methylcyclohexanone, b.p. 164-166' (64yG), from the spiran in the dienone-phenol rearrangement.4s9 oxidation'6 of technical grade 2-methylcyclohexano1, was converted by the procedure of Johnson1' t o 2,6-dimethyl-2The 8,10-dimethy1-2-ket0-A~~~;~.~-hexahydronaphformylcyclohexanone, b.p. 106-112" at 17 mm. (distilled thalene (IX) necessary for the study was synthe- through a 20 cm. Vigreux column), via 2-methyl-&hydroxy sized in an over-all yield of 10% starting from 2- methylenecyclohexanone, b.p. 85-87" at 15 mm. (29YG methylcyclohexanone. The method was an adap- over-all). The procedure used by \Voodwardl to contation of that of Wilds and Djerassi'O employed' vert 2-methyl-2-formylcyclohexanone to 10-methyl-?-lietohydronaphthalene was employed t o obtain the previously. 2,BDimethyl-6-formylcyclohexanone1*A1j9.3,4-hexa cyclohexadienone IX. 2,6-Dimethyl-6-formylcyclohexarion condensation with acetone, with piperidine one, 91.3 g., was dissolved in 800 ml. of dry acetone. Cisacetate as catalyst, then ring closure by meth- tilled piperidine, 53 g., and glacial acetic acid, 37.5 g., were anolic potassium hydroxide gave I X as a solid. added carefully with swirling. The reaction mixture was refluxed 84 hours. The reaction was concentrated on the m.p. 59.5-60.5", , ,X 243.5
