MARTINJACOBSON
4606 [ CONTRIBUTIOX FROM
THE
Vol. T(i
ENTOMOLOGY RESEARCH BRANCH, AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE]
Constituents of Heliopsis Species. 111.
UNITED
STATES
cis-trans Isomerism in Aflinin
BY MARTIN JACOBSON RECEIVED MARCH22, 1954 Treatment of afinin, the insecticidal amide from the roots of Helaopsis Zongipes. with ultraviolet light or with selenium yields all-trans-affinin, which is no longer toxic t o house flies. Proof of structure is shown by hydrogenation t o N-isobutylcapramide and by permanganate oxidation to acetic, oxalic, succinic and N-isobutyloxamic acids. Chemical and spectral data throw light on the stereochemical configuration of the natural isomer and confirm the trans configuration of its conversion product.
yielded about lyOof affinin, the yield after G years was only o.4yO (dry-root basis). The pale-yellow oil obtained boiled a t 157" a t 0.2G mm., n Z 5 D1.5134-, and crystallized in the cold as colorless needlcs, m.p. 23". Exposure of a solution of affinin, in dry petroleum ether containing a trace of iodine, to ultravioCHyCH=CHCH=CH( CH2)2CH=CHCNHCH*CH( CHj)r let light for 2.5 hours gave 5070 of a compound, II C14H23N0, crystallizing as colorless needles, m.p. 0 91.5'. Quantitative hydrogenation to K-isobutylI capramide, m.p. 38-38.5") and oxidation to N-isocompositne), and a detailed report of its insecticidal butyloxamic, acetic, oxalic and succinic acids activity was published b y McGovran, et a1.5 showed it to be isomeric with affinin. The same There are eight possible cis and trans isomers hav- compound could be obtained in 25y0 yield by heating structure I. Although the geometrical config- ing affinin with selenium a t 223" for 2 hours. uration of affinin was not definitely determined, Inasmuch as treatment of a cis compound with ulits failure to yield a maleic a,nhydride adduct sug- traviolet lightlo or with seleniunill has been shown gested that a t least one of the two conjugated dou- to cause elaidinization to the trans isomer, the new ble bonds possesses the cis configuration.6 compound was designated "trans-aflinin." It reatlPrevious work with unsaturated isobutylamides ily gave an adduct, m.p. 1 7 5 O , with maleic anhyhas shown that cis-trans isomerism plays an impor- dride. tant part in their physiological and insecticidal acThe geometrical relationship between affinin and tivity. For example : N-isobutyl-trans-2-trans-4-trans-affinin is borne out by their ultraviolet abdecadienamide caused marked paralysis of mucous sorption spectra (Fig. 1) and infrared spectra (Fig. membranes and was about half as toxic as pyreth- 2) . I 2 The ultraviolet spectra are practically identirins to house flies, while the same compound with cal, both compounds exhibiting the maximum a t a t least one double bond (probably both) possessing 228.5 mp. However, the E value for affinin is 33,the cis configuration was comparatively 700, while that for trans-affinin is 37,100. It has On the other hand, N-isobutyl-trans-L'-trnns--l-dobeen shownI3 that cis and trans isomers usually decadienamide is only weakly pungent and is corn- exhibit almost identical maxima, but that the trans pletely inactive toward house flies.g I t mas there- compound shows a considerably higher intensity. fore of interest to determine the configuration of af- Jackson, et aZ.,l4have found t h a t in the infrared the finin and to prepare and evaluate the corresponding conjugated trans,trans-methyl linoleates are characall-trans compound. terized by a single strong band a t OS8 c m - ' and the The natural affinin used in the present imvestiga- cis,trans isomers by two bands of medium intenstion was isolated b y the procedure previously re- ity a t 948 and 9S2 cm.-'. Evidence along the sanic ported,2from roots of the same batch t h a t had been lines also has been found by Celmer and Solomons" stored in the dark at room temperature for G years. in the case of mycomycin, and by Paschke, et d.li Although roots extracted when first received had This behavior is shown definitely in the case of (1) P a r t I, M. Jacobson, THIS JOURNAL, 73, 100 (1961): p a r t 11, affinin (943 and 976 cm.-l) and trans-affinin 74, 3423 (1952). (98.5 cm.-l only), and is additional evidence The isolation of affinin, an insecticidal amide, from the roots of the Mexican plant submitted as Erigeron afinis DC. and its identification as N-isobutyl-2,G,S-decatrienamide (I), were reported in 1945 b y Acree, et aL2 I n 1947 the plant was shown to be Heliopsis Zongipes (A. Gray) Blake3f4(family
(2) F. Acree, Jr,, M. Jacobson a n d H. L. Haller. J . Org. Chem., 10, 236 (1945); 10, 419 (1945). (3) (a) h l . Jacobson, F. Acree, Jr., a n d H. L. Haller, ibid., 12, 731 (1917); ( b ) E. L. Little, J . Wash. A c a d . Sci., 38, 269 (19481. (4) Although i t was proposed (ref. 3a) t h a t t h e use of t h e name "aninin" for natural I be discontinued, this designation is used througho u t the present paper f o r purposes of convenience. (5) E . R. McGovran, e ' al., U. S. Bur. Ent. a n d Plant Quar. E-736, 5 pp. (1917). (6) T h e Diels-Alder reaction invariably fails or proceeds very poorly when t h e conjugated diene contains a cis bond. See W. D. Celmer a n d I. A. Solomons. T H I SJOURNAL, 76, 1372 (1853), a n d other references cited therein. (7) L. Crombie, Chemistry and I t z d u s l r y , 1031 (1952). ( 8 ) M.Jacobson, T H I SJ O U R N A L , 76, 2584 (1953). (9) hf. J n c o h s o n , unpublished report.
( I O ) (a) R.C. Calderwood and F. D. Gunstone, Cheinislry and I n d u s t r y , 436 (1953); (b) U. Eisner, r t n l . , J . Chem. S o r . . 1372 (I%%!; (c) S. C. Gupta, et a1., J . Sci. Znd. Res. ( I n d i a ) , 10B,7 6 (19311: ( < I 1 P. L . Kichols, e l a l . , THIS JOURNAL, 73, 247 (1931). (11) D. Swern. et al., J . A m . Oil Chemisls' Soc., 27, 17 (1980); J . 11 Skellon a n d J. W. Spence, C h e m i s l v y and I n d u s l v y , 302 (1953). (12) T h e infrared spectra were determined b y Jonas Carol. o f t h e U. S. Food a n d Drug Administration. T h e bands a t 4.10 a n d 4.75 i n r are due t o absorption b y t h e carbon disulfide in which t h e spectra were
prepared. (13) See Cromhie, ref. 7 ; Bisner, ref. lob; H. P. K o c h , Ch?nzirlry a n d Indrrslry, 61, 273 (1042). (14) J. E. Jackson, el a l . , J . A m Oil Chemists' Soc., 29, 22!l (19.72). (1.5) I < . 1'. Pnsclike, W. 'I'olherg an,I n. FI, Wheeler, ihic/., 3 0 , !I7 (IK,3).
cis-trans ISOMERISM IN AFFININ
Sept. 20, 1954
4607
I 36
32
2s
24 m
I
2 x
2c
v IE
12
Fig. 2.-Infrared E
\
4
I
I
I
I
210
230
240
em
260
2x1
zec
Wave length, m p . Fig. 1.-Ultraviolet spectra of affinin (solid line) and trans-affinin (broken line) in 95% alcohol: concentration 2 X 10-6 mole per liter.
for a cis configuration a t the C-6 or C-8 double bond in affinin. The band a t 818 cm.-' in affinin is almost completely absent in the case of trans-affinin. This is in line with Crombie's datal6 for the geometrical isomers of N-isobutyl-2,8-dodecadienamide, showing that a band a t this point is markedly reinforced as one goes from trans,trans to cz's,cis, and may indicate that the a,P-double bond in affinin possesses a cis configuration (an unusual feature in a naturally occurring acid derivative). The same is true for the band a t 725 cm.-' in affinin. In contrast to affinin, which is highly pungent and has the same order of paralyzing action and toxicity to house flies as the pyrethrins, Irans-affinin is only weakly pungent and non-toxic to house flies, but it does exhibit a high paralytic action on this insect. l7 Both isomers show approximately the same degree of instability a t room temperature in the presence of air and light, turning to a darkcolored resin after several weeks. However, they may be preserved a t 5' for a t least a year without deterioration. Experimental'8 Affinh-The natural isomer was isolated in 0.4% yield (based on dry root) from Heliopsis longipes roots stored in the dark a t room temperature for 6 years, by the procedure previously reported.* It was obtained as a pale-yellow, viscousoil, b.p. 157" (0.26mm.), 1 4 l o ( 0 . 2 m m . ) , m.p. 23", 12% 1.5134, Amax. 228.8 m p in 95% ethanol (E 33,700). trans-Affinin.-Affinin ( 5 g.) was dissolved in 30 ml. of Skellysolve B, a small crystal of iodine was added, and the solution was exposed to the direct light from an ultraviolet lamp for 2.5 hours while being cooled with an electric fan t o prevent evaporation. By the end of this period the mixture had crystallized t o a solid waxy mass. It was melted by (16) L. Crombie, J. Chem. Soc., 2997 (1852). (17) T h e t e s t s against house flies were made by W. A. Gersdorff and N Llitlin. (18) .\I1 incltinc ixniits arc COI reclerl, twilini: points are uncorrected.
Wave length in microns. spectra in carbon disulfide: A , aftinin. B, trans-affinin.
warming, 70 ml. of Skellysolve B was added, and the mixture was heated to boiling on the steam-bath. T h e clear yellow solution was separated from an insoluble thick orange oil by decantation, boiled with 1 g. of charcoal, filtered, and concentrated to 30 ml. on the steam-bath. On cooling, a mass of white crystals separated, which was filtered off and washed with a little cold petroleum ether. Four recrystallizations from this solvent gave 2.5 g. (50%) colorless needles, m.p. 91.5'. The compound could be distilled in an atmosphere of nitrogen without decomposition; b.p. 145' (0.25 rnm.), X,, 228.5 m p in 95% ethanol ( e 37,100). Anal. Calcd. for C14H2sNO: C, 76.08; H, 10.49; N, 6.32. Found: C,76.14; H, 10.40; N,6.27. The orange oil (2.28.) insoluble in boiling petroleum ether proved t o be a n intractable resin soluble only in hot pyridine. T h e crystalline compound, m.p. 91.5', could also be obtained by heating 1.5 g. of affinin with 12 mg. of selenium a t 225' for 2 hours, cooling, adding 20 ml. of ether, filtering, and removing the solvent on the steam-bath. Recrystallization of the crystalline residue from petroleum ether gave 375 mg. (25%) of long, colorless needles, m.p. 91.5', and no depression on admixture with the compound described above. The compound (200 mg.), heated a t 100' with 200 mg. of maleic anhydride for 1 minute and then cooled ' gave cry:- , m.D.a 175 talline adduct: colorless needles (from benzene), Anal. Caicd. for CI8HILNOI:.C, 67.68; H, 7.89; N, 4.38. Found: C, 67.54; H, 7.91: N, 4.42. Hydrogenation of trans-Aflinin.-An ethanol solution containing 0.5490 g:of trans-affinin was hydrogenated with 50 mg. of reduced platinum oxide catalyst. I n 15 minutes 158 ml. (cor.) of hydrogen was taken up, and the reaction abruptly ceased. (The theoretical requirement for 3 moles of hydrogen for this weight of a substance of molecular weight 223 is 158 ml.) The reaction mixture was separated from the catalyst, and the solvent was removed a t reduced pressure, leaving 550 mg. of a colorless oil which crystallized in rosettes of needles, m.p. 38-38.5", identical with a specimen of N-isobutylcapramide, m.p. and mixed m.p. 3838.5'. Oxidation of trans-Affinim-To a stirred suspension of 2 g . of trans-affinin in 120 ml. of water, maintained a t 75", 12 g. of finely powdered potassium permanganate (equivalent to 6 moles of oxygen) was added in small portions. When the reaction mixture had become colorless, the manganese dioxide was filtered and washed thoroughly with warm water. The combined aqueous filtrates were concentrated down to 35 ml. and made acid t o congo red with sulfuric acid. The solution was steam-distilled to remove the volatile acids and then extracted with ether in a continuous extractor. The ether solution was freed of solvent, and the partly crystalline residue was subjected t o sublimation in a micro-sublimator. Five hundred and two mg. of colorless solid was obtained, which sublimed a t 100-105° (15 m m . ) and melted a t 185-186' dec. I t reduced rapidly an aqueous solution of potltisium pcrrn,tnganate. and was identified as anhydrous oxalic acid (62'%j by mixed melting point dc-
460s
R.L.LOHMAR
termination with an authentic specimen ( m . p . 156-187' dec.). The sublimation residue, after recrystallization from ethyl acetate, yielded 582 mg. (55%) of colorless crystals, 1n.p. 187-188", identified as succinic acid by a mixed meltine point determination with a n authentjc specimen 187.5-188 .0O ) . The solution of steam-volatile acids obtained above tvvas neutralized .sith sodium hydroxide solution, concentrated to a small volume on the steam-bath, and acidified to red lvith sulfuric acicl, The solution ,vas raaidlv distilled, the distillate neutralized with 0.1 -\'sddiui& hydroxide
Vol. i 6
solution, and the neutral solution evaporated to dryness and the p-phenylphenacyl ester prepared. It melted at 111' and a mixed melting point determination with authentic p phenylphenacyl acetate, m.P. 111O j showed no depression. The distillation residue was extracted with ether in a continuous extractor, and the ether solution was dried and freed of solvent. The crystalline residue sublimed completely a t 90-95" (15 mm.). Recrystallization from Skellysolve B gave 845 mg. (65%) Of colorless feathery needles, m.p. 107", identified as N-isobutyloxamic acid by a mixed melting point determination with a synthetic sample, m.p. 107". BELTSVILLE, MARYLAYD
The Structure of a-Amylase Modified Waxy-Corn Starchlb I~Y I
