March 5, 1053
DECARBOXYLATION OF (Y,P-UNSATURATED MALONIC ACIDDERIVATIVES
yield which when recrystallized from ethanol afforded creamcolored Drisms, m.D. 147-147.5'. Anal.- Calcd. for CcaHssObN: C, 69.85; I I , 6.37; N, 3.54. Found: C, 69.90; H, 6.34; IS, 3.52. 4a ( p Hydroxyethyl) 1,2,3,4,4a,9(and 2,3,4,4a,9,10)hexahydrophenanthrene (XIII and Isomer).-A solution of 4.18 g. of the preceding diol p-nitrobenzoate ( X I ) in 30 ml. of pyridine was treated dropwise while cooling with 5 ml. of phosphorus trichloride and the solution warmed to 50" for 2 hours. The mixture was poured on crushed ice and extracted with chloroform and the extract washed with dilute hydrochloric acid and water and finally dried and evaporated to yield a crystalline mass. Recrystallization from acetonemethanol gave cream-colored blades, m.p. 124-130". Further purification failed to raise or sharpen the m.p. Anal. Calcd. for C23H2304N: C, 73.19; H , 6.14; N, 3.71. Found: C, 73.15; H , 6.11; N,3.73. Saponification was accomplished by heating under reflux for 2 hours a solution of 2.50 g. of the product in.150 ml. of methanol containing 5 g. of potassium hydroxide. Most of the methanol was evaporated, water was added and the product extracted with ether and the extract washed with water, then dried and evaporated. Crystallization of the residue from ether-petroleum ether (b.p. 30-60") gave 1.033 g. (6!% yield) of crystals (XIII), m.p. 84-90', Three additional recrystallizations from ether-petroleum ether afforded fine colorless needles, m.p. 93-100". Further recrystallizations did not alter this m.p. Anal. Calcd. for ClaH200: C, 84.16; H , 8.82. Found: C, 84.29; H , 8.81. 4a-(p-Hydroxyethyl)-1,2,3,4,4a,9,10, loa-octahydrophenanthrene (XIV).-Of the above unsaturated alcohol mixture, 933 mg. was dissolved in 50 ml. of glacial acetic acid and hydrogenated over 200 mg. of platinum oxide under a pressure of 15 lb. p.s.i. of hydrogen. After 20 min. 105% of the theoretical amount of hydrogen was absorbed. The catalyst was reinoved by filtration and the filtrate evaporated t o dryness in vacuo. The residue was dissolved in 50 ml. of methanol containing 5 g. of potassium hydroxide and after standing for one hour the solution was diluted with water and extracted with ether. The ether, after one waterwash, was dried and evaporated to yield an oil which resisted all attempts a t crystallization. It was distilled in wacuo to give 808 mg. of a viscous and colorless oily distillate, b.p. 185-190' (1.5 mm.).
- -
-
[CONTRIBUTIONFROM
THE
*
1163
Anal. Calcd. for CleHz20: C, 83.42; H , 9.62. Found: C, 83.15; H , 9.76. It gave a crystalline p-nitrobenzoate (XV) which after numerous recrystallizations from acetone melted a t 120128'. This m.p. was not significantly altered by additional recrystallization from acetone or other solvent mixtures. Chromatography on alumina was not more successful, all the fractions having similar diffuse m.p. Anal. Calcd. for C2JH2604N: C, 72.77; H , 6.64; N, 3.69. Found: C.72.75; H.6.63; N.3.72. trans-4a- ( p - Dimethylaminoethyl) - 1,2,3,4,4a,9,10,10aoctahydrophenanthrene (XVI).-Seven hundred and fifteen milligrams of the preceding alcohol (XIV) was dissolved in 10 ml. of dry benzene and one ml. of redistilled phosphorus tribromide added. After standing for 3 hours the solution was warmed to 60' for 30 min. and poured into ether which was washed with dilute aqueous sodium hydroxide and water and finally dried and evaporated to yield 517 mg. of an oil which gave a strongly positive Beilstein test for halogen. This was dissolved in 50 ml. of pure anhydrous dioxane and the solution saturated with anhydrous dimethylamine. The mixture was heated to 100" in a sealed tube for 44 hours after which time it was concentrated to a small volume in vacuo and poured into ether. The ether extract was washed with dilute aqueous sodium hydroxide and water and then extracted with dilute hydrochloric acid. The acid extract was made alkaline with aqueous sodium hydroxide and extracted with ether. The ether extract was washed with water and finally dried and evaporated to yield 245 mg. of a yellowish oil. This was treated in a little methanol with 200 mg. of picric acid whereupon 344 mg. of yellow crystals, m.p. 160-180', deposited. Five additional recrystallizations from large volumes of ethanol afforded 96 mg."of large yellow blades with a constant m.p. of 191.5-193 . [Reported5 for N-methylisomorphinane dihydrodesbase picrate: 191-192.5' (cor.)]. I t caused no depression of the m.p, of an authentic sample12 of K-methylisomorphinane dihydrodesbase picrate upon admixture. Anal. Calcd. for C24H?oO7S4: N, 11.51. Found: S , 11.56. Because of the small amount of material obtained, attempts a t the isolation of an isomeric picrate from the mother liquors have not been successful thus far. QUEBEC,QUEBEC
NOYESCHEMICAL LABORATORY, UNIVERSITY O F ILLINOIS]
The Decarboxylation of a#-Unsaturated Malonic Acid Derivatives oia &?-Unsaturated Intermediates. 11. The Effect of a-Substituents upon Product Composition and Rate BY ELIASJ. COREY RECEIVED AUGUST18, 1952 The variation in the relative amounts of a& and B,yunsaturated products formed by the decarboxylation of each of ten malonic acid derivatives (IA-E, IVA-E) in pyridine has been determined. The malonic acids afford the highest proportion of p,r-unsaturated decarboxylation product (over 90%) and appear to be the most satisfactory precursors for the synthesis of p,-y-unsaturated acid derivatives by decarboxylation. Evidence has been obtained from rate data for participation of the carboxyl function in isomerization of a$- to D,y-unsaturated malonic acid derivatives. Both steric inhibition and copper( 11) ion catalysis of decarboxylation via p, 7-unsaturated intermediates have been observed and are discussed.
'
It has been shown recently' that the decarboxylation of ethyl hydrogen isopropylidenemalonate (IC) in pyridine occurs &z the &-punsaturated isomer and affords a mixture of a,p- and P,runsaturated products (25% IIC and 75% IIIC) both of which are stable under the reaction conditions. Since a knowledge of the relationship between the substituent X in compounds of type I (X = CN, CONH,, COOH, CON(CH&) and product composition is necessary for the evaluation of decarboxylation as a synthetic route to B,r-unsaturated acids and acid derivatives, we have (1) E. J. Corcy, T m Joomru,T4, 6887 (1063).
I A, = CN B, x = C O N H ~ C, x = C O O C ~ H ~ D, X = COOH H3c>=C(z = CoN(CHs)p I1
+ :l>C-CH&
E*
I11
investigated the change in the ratio of a,@-to @,yunsaturated decarboxylation product for the series IA-IE. In addition, a parallel series of B,r-
ELIASJ. COREY
1164
unsaturated acid derivatives of type I V has been studied. The effect of the group X upon both product composition and rate of decarboxylation is obviously also of interest from a theoretical viewpoint. ;>C-gOoH
A, X B,X C, X D, X E, X
---f
CH3 IV = CN = CONHI = COOCnH6 = COOH = CON(CH3)z
Vol. 75 TABLE I
Compound
IA IB IC ID IE
Product (5% B,r-isomer in a$ f @,r- Rate constant, mmture) kl, min.-'
SOaib
tab
75"'d 93" 2gh
0.028 ,024 .02 ,067' .OOl
Temp.,
OC.
111.0
IVA sob 3.0 IVB 72' 0.5 IVC 5Oosd .05 95.0 IVD 95" .092' IVE gob .02 Analyzed by infrared a Analyzed by refractive indices. spectra. Uncorrected for statistical effect of two carboxyl groups. Cf.ref. 1.
Neither the amides IB and IVB nor the esters IC and IVC can be regarded a more satisfactory precursors than the corresponding nitriles for the production of 8,y-unsaturated acid derivatives. It is worthy of note, however, that decarboxylation of the a,p-unsaturated half amides and half esters IB and IC leads to a higher proportion of Plyunsaturated product than does decarboxylation of the 0, y-unsaturated derivatives IVB and IVC. The Acids ID and IVD.-It is clear from Table I that the malonic acids I D and IVD afford relatively more of the p, y-decarboxylation product than do their derivatives. Hence, a,@-unsaturated Discussion malonic acids appear to be the most satisfactory The Nitriles, Amides and Esters.-Both the precursors of p, y-unsaturated acids and acid nitriles studied (IA and IVA) yield the same high derivatives. proportion of p, y-unsaturated isomer upon deA second point of significance emerges from the carboxylation. If the only route available for the rate data. The rate constant for the decarboxyladecarboxylation of IA is via the p,y-isomer IA', tion of the a,@-unsaturatedmalonic acid I D (allowit is apparent that the presence of an a-methyl ing for a statistical factor of 2) is larger than those substituent in IVA instead of a hydrogen (as in for the a,p-unsaturated derivatives IA, IB and IC, IA') is not sufficient to affect product composition. whereas the rate constant for the decarboxylation Since the structural considerations which argue of the p,y-unsaturated malonic acid IVD (allowing against the possibility of facile direct decarboxyla- foi a statistical factor of 2 ) is smaller than those for tion of a,@-unsaturatedmalonic esters, amides, etc., any of the other 0, y-unsaturated compounds IVA, do not apply in the case of the nitriles,2 the de- IVB and IVC. This fact suggests the possibility carboxylation of pivalylidenecyanoacetic acid (VII) that a statistical factor of 2 is operative not only which is incapable of isomerization to a P,y-un- in the decarboxylation of the 6,y-unsaturated acids, saturated intermediate was studied to determine the but also in the conversion of the a$-unsaturated ease of direct decarboxylation. The rate constant for compound I D to the p,y-isomer. In turn, the the decarboxylation of VI1 in pyridine at 111' operation of a statistical factor for the isomerizais 0.14 times that of IA and the product of reaction tion signifies participation by the carboxyl function is trans-p-t-butylacrylonitrile(VIII) (also formed in this step. A reasonable interpretation of the by heating VI1 a l ~ n e ) . ~ It is possible, therefore, isomerization factor may be derived on the basis of that IA decarboxylates to a small extent by a the finding in previous work' that the rate-deterdirect mechanism mining step for the a,P -+ p, y-isomerization of IC is the abstraction of a proton from the y-carbon of (CH,)~CC!H=C
