[CONTWBUTION PROM THE
n'OYES CHEMICAL
LABORATORY, IJNIVERSITY
OF ILLINOIS]
The Structure of Monocrotaline. 111. Monocrotalic Acid' BY ROGERADAMS.E. F. ROGERSAND R , S. LOW$
On catalytic hydrogenation of monocrotaline, two moles of hydrogen are absorbed with formation of an alkanolamine, retronecanol, and an optically active acid, C*Hl2O5,called monocrotalic acid. CtsHz80eN 4- ZHI --+ CsHtrON $. CSHtzOs Retronecanol
Monocrotalic acid
Monocrotalic acid (I) contains one carboxyl group. On back titration of the acid from excess alkali, the presence of a lactone group is indicated. The acid gives a crystalline monomethyl ester (11) with diazomethane which shows one active hydrogen by a Zerewitinoff determination. Esterification of the acid with methanol and sulfuric acid was unsuccessful and only a very poor yield of ester was obtained with methanol sattirated with hydrogen chloride. The acid decomposes on heating past its melting point to give an optically inactive neutral compound, C7H1002(I11 or IX), which is identical with a,fl,y-trimethylangelicalactoneobtained by dehydration of monocrotic acid, C7H1203 (IV or VIII). The same lactone can be obtained by a twostep procedure which clarifies the reaction. Methyl monocrotalate (11) on heating i n zmuo loses water to give an unsaturated ester (C7H902)COOCH3 (Vi, together with a small amount of lactone (111). This ester reduces acid permanganate and can be hydrogenated under high pressure to a dihydro ester (VI) which in turn may be (C7H1103)COOH I 1 - COZ -H20 j,
--------+ (CyH1103)COOCHs r1
1
Y
(CrHsO2)COOCH,
I11
f
(CBHIIO) COOH IV
--02
(C,Hn02)COOCH3
I''
JHCI
(CrHiiOdCOOH VI1 (1) For previous paper see Adams, Rogers and Sprules, T H I ~ 61,2819 (1939). (2) An abstract of a thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in chemistry (3) Adams and Rogers, THISJ o r ' m h L , 61, 2815 (193% JOURNAL,
hydrolyzed to a crystalline lactonic acid, (C7H11Os)COOH (VII). The unsaturated ester (V) on hydrolysis with concentrated hydrochloric acid, yields the same lactone, C7Hla02 (111), which is obtained by thermal decomposition of monocrotalic acid. It is obvious then that upon heating monocrotalic acid two reactions occur, dehydration and decarboxylation. These reactions just discussed are shown in tabular form. The above observations show that monocrotalic acid contains a lactone group which, while stable to heat and strong acid, cleaves readily with alkali to give an unstable, easily decarboxylated acid which could not be isolated. The ease of dehydration of monocrotalic acid and especially of its methyl ester is best explained by the presence of a tertiary hydroxyl group. I t has been demonstrated' that the acid obtained by alkaline hydrolysis of monocrotalic acid is a,fi-dimethyllevulinic acid (VIII). 0 I/
CHI-~C-CH~
CHrCH-C-CH3
I
I
i
>o
CHr--CH-CO IX
CHs-CH-COOH
VI11
Since IV has the structural formula VIII, it follows that the corresponding lactone (111) must be a,fl,y-trimethylangelicalactone(IX) which was obtained by the dry distillation of monocrotalic acid (I). Three structures of monocrotalic acid (I) may be considered, XI, XI1 and XIII. Structures XIV, XV and XVI would then represent, respectively, the anhydromonocrotalate (V). AI1 three of these structures have as a common feature the grouping
OH
0
=c--Q-c-I/ I
which explains
the smooth formation of a keto acid on breaking the lactone ring. The structures differ in the position given the free carboxyl group. Structure XI11 appears unlikely due to the fact that monocrotalic acid is esterified with acid and methanol only with great difficulty. This is indicative of a tertiary carboxyl. Structure XI11 should not decarboxylate as readily on heating as was actually observed. Moreover, methyl anhydromonocrotalate does not give a Legal test al-
Oct., 1939
2823
MONOCROTALIC ACID OH
I
CHrCH-C-CHs
COOH OH
I
I
I
>
CHrC--.---C-CHs CH-CH-CO
OH
I
CHrCH-C-CHzCOOH
COOH
XI
XI1
XI11
CH3-bC-CHa
CH--C==C-CH?COOCH3
CH3-C-CO
CH-CH-CO
I >
I >
I
COOCHs XIV
xv
though the unsaturated ester (XVI) derived from an acid of structure XI11 should do so, since this test is specific for 0,y-unsaturated y-lactones containing a free hydrogen in the a-po~ition.~On the basis of this evidence, structure XI11 may be excluded. The degradation of monocrotalic acid (I) with alkali goes smoothly and quantitatively to monocrotic acid (VIII).3 This reaction proceeds equally well whether dilute or concentrated alkali is used. Unquestionably the first step in the degradation is the formation of the salt of the tautomeric keto acid. Thus, XI1 would be converted to XVII, which is a 0-ketonic acid. A difference COONa
I / / I
CHrC-C-CHs
CH8-CH-COONa XVII
in the decarboxylation products should result whether diluted or concentrated alkali is used, for the former should give a ketone splitting to a levulinic acid derivative, whereas the latter should give a t least partially an acid splitting with formation of a a,a'-dimethylsuccinic acid. None of the latter product could be isolated. Methyl anhydromonocrotalate can be reduced catalytically only under high pressure. This fact is better reconciled with a substituted angelicalactone of formula XIV rather than XV. It is concluded, therefore, that formula XI represents the most likely structure for monocrotalic acid, namely, a-carboxy-a,8-dimethyl-y-hydroxyy-valerolactone. It explains also the presence of one active hydrogen in methyl monocrotalate. On this basis, the other degradation products would have the structures: hydrogenated methyl (4) Jacobs and Hoffman, J . B i d . Chcm.. 61, 333 (1925).
XVI
anhydromonocrotalate (XVIII) and its acid hydrolysis product (XIX). C H r CH-CH-CHs
I >
CHrC-CO II
C H r CH-CH-CHs
'P
CH-C- I
0
I
COOCHs XVIII
COOH XIX
Monocrotalic acid and all of its derivatives in which the carboxyl group is intact are optically active, whereas the lactone obtained from monocrotalic acid or its derivatives is inactive due probably to its ease of enolization.
Experimental Methyl Monocrota1ate.-To a suspension of 5 g. of monocrotalic acids in 30 cc. of chloroform was added slowly with stirring an ether solution of diazomethane until a slight excess was present as evidenced by a yellow color in the solution. The temperature was not allowed t o rise above IO'. Evaporation of the ether and chloroform under diminished pressure left a n oil which crystallized rapidly. The product was purified by recrystallization from ether: white crystals, m. p. 79-80' (corr.); yield, 5.17 g. (97%). Anal. Calcd. for CsHl4Os: C, 53.47; H, 6.93. Found: C, 53.87; H, 7.09. Rotation. 0.502 g. made up to 10 cc. at 30" in absolute ethanol. or^ -1.63; 1, 2; [or]aoD -16.24'. A Zerewitinoff determination showed 1.18 active hydrogens. Heat Decomposition of Monocrotalic Acid: a,@,?Trimethylangelicalactone.-In a small modified Claisen distilling flask immersed in a Woods' metal bath was placed 15 g. of pure monocrotalic acid. Heat was applied and, a t a bath temperature of 200 ', the evolution of carbon dioxide and water was apparent. When this had ceased the bath was cooled and the residue distilled: colorless liquid, b. p. 82-83' (1 mm.); dZ94 1.024; n z o 1.4664; ~ yield, 8.6 g. (86%). Anal. Calcd. for CTHIOO~: C, 66.67; H, 7.94. Found: C, 66.45; H, 8.04.
Methyl Anhydromonocrotalate. I n ,* sninli I J I ~ I I I ~ I C Claisen distilling flask 1.5 g of methyl nionoLiolalate was heated a t 200-210" until the cvolution of water waq ompietc Fiactioiiatioii ~f the rtsiidut gave 4 3 i: 01 material, b. p L U G 1 1.7 ( 3 iiirii , and 7.5 g of pule inc,hqI anhydronionocrotalatt 1 s i 1 7 I lr ' itiIri v-'i-i 1 G O O , d3-4 I 131 Anal. Calcd. for CgHSJO,. C, 68 7 0 H r i 3 Found C, 58 83, FI, 8 82 Rotatzon (Pint liquid ar 3 0 &>P I, 2, IN ! J % 4-23 74 A wcond fractionation of the low boiling portion gavc ! 8 g of low- boiling material and 1 7 g of pure methyl dnhydroilionocroldatr Further purification of t h c lox% boding material from tliii distillation gave t) 5 g of p u r t ~y,p,ytrimethylangelicalactone identical with that 01,tained directly from iiioiiocrotalic acid, 17 J) 93" r n m 1, nZaD 14658 d n d Calcd for C-H,oO C, WI B i , H, 7 '41 Found C, ti6 10, H, 8 02 Hydrogenation of Methyl Anhydromonocrotalate and L~,$,~-Trimethylangelicalactone: u-Carbomethoxy-a,pdimethyl-r-valerolactone and a,/.3-Dimethyl--i-valerolactone.--Ynfractionated inethyl atihydronionociotalate ( 9 g I containing a,&y trirnethvlangelicalactone was dissolved i n 70 cc of ethei and hydrogenated at 2200 pound.; (167 atni ) and 125" using Raney nickel as the catalyst Tlir theoretical amount of liydrogeii was absorbed and t l t c residue, after removal of the ether, was carefully frac tionated, yield, 0 8 g of CU,?-dimethyl-r-valerolactone, 1,. p 67-69" ( 2 irini 'i. IZ"D 14382, dL940 987, and R 0 of hydrogenated methyl anhydromonocrotalate, h J J 115--117' (1 niin j , ) Z ~ " Di 4510, dZy4 (J 9% Anal i~,d-Dimethyl-r-valerolactoneI Calcd for C7HI2O2. C, 6563, H, 938 Found C, 6343, H, B 57. (Hydrogenated methyl anhydromonocrotalate Calcd for C9HI&: C, 53 06 H 7 *53 Found C W 0 9 , H, 7 7 0 Rotation (Pure Iiquic! ,if 20" r u ~ A l l 1 t5 7. A ~cY]''D +560 When pure methyl anhydrornonocrotalatc was hydrogenated undei similar conditions, a pure reduced product was obtained with con\tantc. identical with thoye lust described Hydrolysis of Dihydromethyl Anhydromonocrotalate: cr-Carboxy-a,p-dimethyl--,-valerolactone.-a4 mixture ol 4.6 g. of dihydromethyl anhydromonocrotalate and 20 cc of concentrated hvdrochlorir acid was refluxed for five I
Evaporation of the water under reduced pressurc ~ hours. ~ left 2.7 g. (63%) of crude acid which after purification by recrystallization from benzene gave 2.6 g. of pure acid: .tals. ni. p. 131-132' (con-.). .4na8. Calcd. for C&T&i: C, 65.81: H, 6.98. Found:
c. S$,e'J?;
f-f, f ~ \ . ~ ~ 8 , Xotc~finn. 0.303 g. made up to 10 cc. of absolute ethanol at 30'. CUD+0.23; 2, 3 ; [ a ] " D +3.80". Thc p-broinophenacyl ester was prepared from 0.1 g. of the acid and an equivalent amount of p-bromophenacyl brornidc according to the standard procedure. Purified from ethanol it formed white crvstals, in. p, 142--113" tcorr,\: yield, (1.12 g. i37%'1 .lt7ul, Calcd. for C1~H~,ObBr: C , 52.03, H, 4.61. Found: C, 52.33; H, 4.91. Rotation,. 0.2313 g. made up to 5 cc. in acetone a t 29".
