ALLETHRIN. RESOLUTION OF dl ... - ACS Publications

F. B. LaFORGE, NATHAN GREEN, and M. S. SCHECHTER. J. Org. Chem. , 1954, 19 (3), pp 457–462. DOI: 10.1021/jo01368a027. Publication Date: March ...
0 downloads 0 Views 426KB Size
[CONTRIBUTION FROM THE UNITED STATEBDEPARTMENT OF AGRICULTURE, AGRICULTURAL RESEARCH SERVICE, BUREAUOF ENTOMOLOQY AND PLANT QUARANTINE]

ALLETHRIN. RESOLUTION OF dl-ALLETHROLONE AND SYNTHESIS OF T H E FOUR OPTICAL ISOMERS OF trans-ALLETHRIN F. B. LAFORGE, NATHAN GREEN,

AND

M. S. SCHECHTER

Received August 31, 1963

Allethrin is a mixture of esters of dl-allethrolone with dl-cis- and dl-transchrysanthemumic acids (1). There are eight optically active stereoisomers possible, four having a cis-acid component and four having a trans-acid component. In this article, the preparation of the latter four esters will be described, while the esters having the cis-acid components will be described in a future article. For simplicity, the various isomers of allethrin will be designated according to the optical characteristics of the allethrolone and the acid components. Thus d-allethrolone d-trans-chrysanthemumate will be designated as d-d trans-allethrin. The structural formula of allethrin is as follows: CHI

I

HaC-C=O

t

The insecticidal mixture of these esters may be compared with the isomers of benzene hexachloride, only one of which is mainly responsible for its insecticidal properties. In the case of allethrin it is also reasonable to assume that its characteristic knockdown and insect toxicity are associated to a greater or lesser degree with certain of the several isomers present (2, 3, 4). In fact, there is evidence already at hand that optical activity is of paramount importance with respect to the chrysanthemumic acid component, only the d-acid esters showing high insecticidal action, those of the 2-acid being practically nontoxic (5). In the case of the pyrethrins and cinerins, the acid as well as the cyclopentenolone components are dextrorotatory ( 6 ) , and these optical forms probably give the maximum obtainable insecticidal effect. The dl-allethrolone ester of d-trans-chrysanthemumic acid has been shown to be about twice as toxic to house flies as the allethrolone ester with dl-transchrysanthemumic acid (2). To establish quantitatively their relative insect toxicity, it seemed necessary to prepare and test all the optical isomers of allethrin. The preparation of the four optically active isomeric d- and 1-allethroloneesters of d- and 1-trans-chrysanthemumic acids has now been made possible with the resolution of dl-allethrolone by the procedure described in this article. This procedure follows in general that employed in the resolution of dl-cinerolone (7). Natural d-trans-chrysanthemumic acid was esterified with dl-allethrolone, 457

458

LAFORGE, GREEN, AND SCHECHTER

and the ester mixture was treated with semicarbazide to form the ester semicarbazones. The semicarbazone of d-allethrolone d-trans-chrysanthemumate was isolated from the more soluble semicarbazone of 1-allethrolone d-trans-chrysanthemumate by crystallization from ether-petroleum ether mixtures. However, the separation is complicated by the fact that the latter ester-semicarbazone and its mixture with the former also crystallize. Therefore, a more careful adjustment of the proportions and quantities of the solvents was necessa,rythan in the resolution of dl-cinerin I. Methanolysis of the pure d-allethrolone d-trans-chrysanthemumate semicarbazone furnished the semicarbazone of d-allethrolone, which was hydrolyzed in the usual manner with aqueous potassium bisulfate to free dallethrolone. The partially resolved allethrin semicarbazone remaining after separation of d-allethrolone d-trans-chrysanthemumate semicarbazone, in which E-allethrolone d-trans-chrysanthemumate semicarbazone predominated, furnished, by this sequence of treatments, a mixture of the 1- and dl-allethrolones. This mixture, when acylated with 1-trans-chrysanthemumicacid, yielded predominantly Z-allethrolone Z-trans-chrysanthemumate,with a smaller proportion of d-allethrolone 1-trans-chrysanthemumate. The semicarbazone was obtained by crystallization from ether-petroleum ether mixture as described above for its opposite isomer. It was the source of 1-allethroloneprepared via its semicarbazone obtained by methanolysis. Acylation of the d- and 1-isomeric forms of allethrolone with d- and l-transchrysanthemumic acid, respectively, furnished the four optically active transacid isomers of allethrin. Previous attempts to hydrolyze the semicarbazones of allethrin or of the analogous mixtures of the pyrethrins group by the procedure that is successful with the cyclopentenolone semicarbazones have failed, owing, we believe, to their complete insolubility in aqueous acid media. It has now been found possible to achieve such a hydrolysis with a fair (ca. 60%) yield of pure distilled ester by agitation with a 50% aqueous acetic acid mixture containing about 7 to 8% of sulfuric acid. The reaction is accompanied by some hydrolysis of the ester to chrysanthemumic acid. No dimer (8) formation was observed. Since the byproducts are easily removed, the method permits the preparation of chemically and optically pure d-allethrolone d-trans-chrysanthemumate and the optically opposite isomer where the corresponding pure semicarbazones are available. A crystalline racemic form of allethrin which sometimes separates from the synthetic product has been reported (4) and was indicated to be a racemic compound of either d-allethrolone d-trans-chrysanthemumate and Z-allethrolone 1trans-chrysanthemumate or of d-allethrolone l-trans-chrysanthemumate and 2-allethrolone d-trans-chrysanthemumate. With the accessibility of the optically active forms, it was possible to prove that the crystalline racemate consisted of the latter pair of isomers. Upon mixing the two requisite optically active isomers in equal quantities and seeding, the crystalline alpha-dl-trans isomer was obtained. Other optical members, either alone or in mixture, showed no tendency to crystallize.

ALLETHRIN

459

EXPERIMENTAL

Semicarbazone of d-d trans-allethrin (d-allethrolone d-trans-chrysanthemumte) . dl-Allethrolone (27.2 g., 0.18 mole), ni5 1.5168, was esterified with 34 g. (0.18 mole) of d-transchrysanthemumic acid chloride in the usual manner to yield 53 g. of the ester, from which the semicarbazone was prepared. The quantities of reagents were semicarbazide hydrochloride (25 g,), water (30 ml.), pyridine (20 ml.), and 95% ethanol (180 ml.). After about 18 hours most of the ethanol was removed in a vacuum, water was added, and the semicarbazone was extracted with ether. The ether solution was washed with water, dilute acid, and finally with salt solution until free of ethanol. After the solution had been dried with potassium carbonate, the volume was reduced to 120 ml. Crystallization, which had already begun on cooling t o about 40", was completed by the slow addition of about 100 ml. of low-boiling petroleum ether. After a short time in the refrigerator, the separated aemicarbazone was filtered off with light suction and washed with a 50-50 mixture of dry ether and petroleum ether. The filtered product was generally suspended in the solvent mixture and again was filtered and washed with petroleum ether. Freed from solvents by keeping in a vacuum, the compound had no sharp melting point (68-75").1 Yield, about -150" (in methanol, c, 4.5). 16 g., Anal. Calc'd for CzoHzoNsOs: C, 66.82; H, 8.13; N, 11.69. Found: C, 67.10; H, 7.82; N , 11.74. In another experiment, where the quantities were 47 g. of d-trans-acid chloride and 37.5 g. of dl-allethrolone, the yield of d-d trans-allethrin semicarbazone was 22 g., [a]i5146". The residue obtained after evaporation of the solvents from the ether-petroleum ether filtrates and washings, in which the semicarbazone of 1-d trans-allethrin predominates, was the source of 1-allethrolone semicarbazone as described below. d-Allethrolone semicarbazone. In a solution containing 1.0 g. of sodium in 90 ml. of methanol plus 0.85 ml. of water was dissolved 16.9 g. of d-d trans-allethrin semicarbazone. The mixture was kept in the refrigerator for 5 days with occasional shaking. The solution decanted from the crystalline material was concentrated t o a small volume by means of a stream of air and then diluted with water; after standing for a few hours, the separated material was filtered off and washed with water and then with ether. The combined solid material was recrystallized by dissolving in boiling ethanol, filtering from a small quantity of insoluble material (dimer semicarbazone) (8), and concentrating the filtrate to incipient crystallization. The compound melted a t 214-216", [a]?-166" (c, 1.8 glacial acetic acid). Anal. Calc'd for C10H16Na02:C, 57.40; H, 7.23; N, 20.08. Found: C, 57.76; H, 7.06; N, 19.32. The first aqueous filtrate and ether washings contain the methyl ester and a small amount of the sodium salt of d-trans-chrysanthemumic acid, from which the acid is subsequently recovered. d-Allethrolone. d-Allethrolone semicarbazone (9.1 g.) was suspended in 100 ml. of water containing 50 g. of potassium acid sulfate together with 75 ml. of ether and was shaken for six hours a t room temperature. Longer treatment is to be avoided because of a tendency toward racemization. The aqueous solution was saturated with salt, and the separated ether solution was washed once with the minimum amount of salt solution because the free allethrolone is somewhat soluble in water. The residue from the ether solution was distilled; b.p. 103-107"/0.15 mm., n:' 1.5150, [a]:' 7.3" (e, 13.5 in ethanol, 4-dm. tube); +8.6' (without solvent). Anal. Calc'd for CgH1202: C,71.02; H, 7.95. Found: C, 70.10; H, 7.84. Semicarbazone of 1 4 trans-allethrin (1-allethrolone 1-trans-chrysanthemumate). The combined residues, 75 g., from the ether-petroleum ether filtrate obtained in the preparation

+

1

All melting points are corrected.

460

LAFORGE, GREEN, AND SCHECHTER

of d-d trans-allethrin semicarbazone as described above were dissolved in 400 ml. of cold methanol, and a cold solution of 4.8 g. of sodium in 100 ml. of the same solvent containing 3.8 ml. of water was added. After standing for five days a t about 4', the semicarbaeone of Z-allethrolone containing some dl-allethrolone was isolated and recrystallized in the same $49" manner as described above for d-allethrolone semicarbaaone giving a product (c, 5.5 in glacial acetic acid). This material was hydrolyzed by mechanically shaking 23 g. with 120 g. of potassium acid sulfate, 240 ml. of water, and 760 ml. of ether for six hours. The free allethrolone was isolated from the ether solution and distilled, b.p. 120-125"/@.3 mm., yield 14.3 g. (85%), [a]i5-2.75" (without solvent). The 14.3 g. of this partially resolved allethrolone was esterified in the usual manner, the proportions employed being 17.5 g. of I-trans-chrysanthemumic acid chloride (from 1-trans-acid having [a]:5 -20.1', without solvent) (9) and 8 ml. of pyridine, in benzene solution. The yield of 1-1 transallethrin (containing a small amount of I-d trans-allethrin) freed of solvent in a high vacuum was 27.7 g. The semicarbazone was prepared and treated as described above for the preparation of d-d trans-allethrin semicarbazone, and the dried ether solution was concentrated t o 100 ml. Since it was present in large proportion, the semicarbazone of I-l trans-allethrin began t o crystallize at once from the concentrated ether solution, and the addition of only 25 ml. of petroleum ether to the cooled mass was sufficient t o complete the crystallization. It was necessary, however, to add about 75 ml. of a 50-50 ether-petroleum ether mixture to facilitate filtration and washing. Yield 12.1 g., [a]z5$150' (c, 8.0 in methanol). Anal. Calc'd for C2oHZ9NsOs:C, 66.82; H, 8.13; N, 11.69. Found: C, 64.05; H, 7.68; N , 11.47. Semicarbazone of 1-allethrolone. 1-1 trans-Allethrin semicarbazone, 23 g., was subjected t o methanolysis under the conditions employed in the instance of its antipode, 1.35 g. of sodium, 1.1g. of water, and 120 ml. of methanol being used. The recrystallized product melted a t 215-218" with decomposition; [a]:' +167" (e, 1.8 in acetic acid). Anal. Calc'd for CloHlsNaOZ: C, 57.40; H, 7.23; N, 20.08. Found: C, 57.49; H, 6.83; N, 19.31. I-Allethrolone. The semicarbazone (12 g.) was hydrolyzed with aqueous potassium acid sulfate and the free ketone was isolated as described for the d-isomer, b.p. 106-110"/0.15 mm., ni' 1.5141, -6.7" (c, 16 in ethanol); -8.7" (without solvent). Anal. Calc'd for CoHlzOz: C, 71.02; H , 7.95. Found: C, 69.95; H, 7.80. All four optical isomers of the trans-chrysanthemumic acid series were prepared by the

TABLE I OPTICALLY ACTIVEESTERS O F ALLETHROLONE WITH tranS-CHRYSANTHEMUMIC ACID

n%

d de d 1

1

lC 0

ANALYSIS~

OPTICAL PROPERTIES

ALLETHRIN

1.5050 1.5047 1 .5047 1.6046 1.5040 1.5034

j

[a]%

C

-19.4 -22.3

74.78

f22.4

75.56

-22.6 +17.0 +20.9

i 1

'5," i ____________

H

8.41 8.51

8.62

-

I n purified kerosene (Deobase) c, 16.

' Calc'd for C1DH560~:C, 75.46; H, 8.67. Prepared by sulfuric-acetic acid method, all others were prepared by resynthesis.

ALLETHRIN

461

usual method of esterification of the d- and 1-forms of allethrolone with the d- and 1-forms of the acid, respectively, as fOllOw6. d-d trans-Allethrin. T o 3.0 g. of d-allethrolone in ca. 15 ml. of benzene plus 2.0 ml. of pyridine was added a benzene solution of d-trans-chrysanthemumic acid chloride (3.9 g.), prepared from the pure d-trans-acid. After standing for about 18 hours, the mixture was washed in a separatory-funnel with dilute acid and with dilute sodium carbonate solution, the solvent was removed in a vacuum, and the residue was distilled; b.p. 130-135"/0.07 mm. The other three optical isomers were prepared in exactly the same manner with the same quantities of reactants and reagents. Their properties are shown in Table I. The d-d and 2-2 trans-allethrins were also prepared by direct hydrolysis of the corresponding semicarbazones. d-d trans-Allethrin by direct hydrolysis of the semicarbazone. d-d trans-Allethrin semicarbazone (8.0 g.) was shaken for 18 hours with a mixture of 45 g. of glacial acetic acid, 50 ml. of water, and 7 ml. of concentrated sulfuric acid. The reaction mixture, after saturation with salt, was extracted with petroleum ether. The upper layer was washed repeatedly with water until free of acetic acid. It was then extracted with sodium carbonate solution, from which 0.8 g. of chrysanthemumic acid was recovered. The residue from the dried petroleum ether solution was distilled. After a small forerun (ca. 0.5 g.), the main fraction distilled a t 135-138"/0.05 mm. The yield of allethrin in this and similar experiments was about 60%. 1-1 trans-Allethrin by direct hydrolysis of the semicarbazons. 1-1 trans-Allethrin semicarbasone (12 g.), was shaken for 18 hours with 45 ml. of acetic acid, 45 ml. of water, and 7 ml. of sulfuric acid, and the reaction products were worked up as described for the d-disomer. The product, 5.2 g. of 1-I trans-allethrin, distilled a t 135-138"/0.05-0.1 mm. after 1.9 g. of a forerun had been collected up t o 135". Crystalline allethrin racemate. Equal parts of d-1 trans- and 1-d trans-allethrin crystallized when mixed and seeded with the alpha-dl-trans-isomer of allethrin (4). The product was recrystallized from petroleum ether and then melted at 50.5-51". When it was mixed with the alpha-dl-trans-isomer of allethrin there was no depression of the melting point. SUMMARY

dl-Allethrolone has been resolved into its d and I forms by a procedure involving esterification with d-trans-chrysanthemumic acid (via the acid chloride), formation and fractional crystallization of the semicarbazones of the mixed diastereoisomeric esters, methanolysis of the separated ester semicarbazones, and cleavage of the optically active d-allethrolone from its semicarbazone. Although d-allethrolone can be obtained pure by this method, the l-allethrolone is not pure and must be esterified with Z-trans-chrysanthemumic acid (via the acid chloride) and the procedure of separation of the semicarbazones, methanolysis, and regeneration of the ketone must be repeated. Each of these optically active allethrolones was esterified with d- and I-trans-chrysanthemumic acids respectively to give four of the eight possible optically active isomers of allethrin. A crystalline isomer of allethrin previously reported has been determined to be a racemic compound of d-allethrolone I-trans-chrysanthemumate and 1-allethrolone d-trans-chrysanthemumate. A procedure has been developed for splitting semicarbazone derivatives of allethrin isomers which does not cause extensive hydrolysis of the ester linkage. BELTSVILLE, MD.

462

UFORGE, GREEN, AND SCHECHTER

REFERENCES

(1) ROARK,A Digest of Information on Allethrin, U. S. Bur. Ent. and Plant Quar. E-846 (1952). (2) GERSDORFF, Soap Sanit. Chemicals, 26, 129 (1949). J . Econ. Entomol., 42, 532 (1949). (3) GERSDORFF, LAFORGE, ZIMMERLI,AND THOMAS, J . Am. Chem. SOC.,73, 3541 (1951). (4) SCHECHTER, GERSDORFF, GREEN,AND SCHECHTER, J. Org. Chem., 17, 381 (1952). (5) LAFORQE, (6) LAFORQE AND BARTHEL, J . Org. Chem., 12, 199 (1947). (7) LAFORQE AND GREEN,J . Org. Chem., 17, 1635 (1952). (8) LAFORQE, GREEN,AND SCHECHTER, J . Am. Chem. SOC.,74,6392 (1952). (9) CAMPBELL AND HARPER, J . Chem. SOC.,283 (1945); J . Sci. Food Agr., 4, 189 (1952).