Pyrethrum Flowers
In Production of Ethyl Diazoacetote, O p e r ators Perform All Operotionsfrom Behind a
14-Inch Reinforced C w r e t e Barricade
I c
A STAFF-INDUSTRY COLLABORATIVE
REPORT
HOWARD J. SANDERS, Associote Mitor in collobomtion with
ALBERT W. TAFF Baltimore, Md.
U. S. lndustriol Chemicals Co.,
ALLETHRIN ARCH 11, 1949, a leading spokeaman for the U. 8. t of Agriculture's Bureau of Entomology and tine formally anwunoed a major achievementin the cidal research. T o representativen of the praee, that three UBDA chemists had a u d M y carried a of not only one of the mokc0mplex valuable insecticides ever developed. boratory in Beltsville, Md., LaForgt., performed the 6r8t total 'synthenis d a named allethrin. achievement wae promptly heralded in wores of trade and al journals .throughout the world. T h e ayntheais d WM acclaimed an a major mileetone in the field of chem-mmDl)rable in imoortance to the develooment of rubber. ativelv new insecticide is the allvl homoloe dr cinerin I. ch-cal ditIereoce between .ðrin a i d cinerin I, steraochemical coneiderations, is that in allethrin the p i e replaced by an allyl side-chain. Cinerin I, in the four active components imlated thus tar from al inaeoticide, pyrethrum. the beginuing, the hiatoFJr of allethrin has been intimately with that of pyrethrua Allethrin, in fact, was developed 88 a meana of supplementing 'the world's
414
limited supply of pyrethrum. Thie latter inaecticide is obtained from pyrethrum flowers, which, SimIlSr in appearance to daieiea, are UW&EI of the chryesnthemum f h i l y . Approximately 1.0 to 1.5% by weight of dried pyrethrum flowers& recovered as the effeotive insecticide (8). The UBB of pyrethrum in Europe began in the early 1800's. The oommmial W r y of p y r e t h , however, dates back only to about l9l8, arhen a k p e b e extract of pyrethrum flowera waafdund to be highly potemt 88 a spray againat flie?, m o e q u i k , and other inaecte. Pyrethrum, i t waa discovered, not only dvea quick kuockdown and kill hut, in normal use, is completely free of ' It is, therefore, quite safe for toxicity to man and animals (W). household application and for uee on foods, grains, animals, and on field mpa immediately before hameet. Despite these compelhg advantage+ pyrethrum suflers from several major handicaps, not the least ofwhich is ite limited, nnstable supply. The economical cultivation of pyrethrum flowers requires a highly favorable combination of climate, soil, elevation, land coat, and labor c o s t c o u d i ~ i o n that s are found in very few parte of the world. I n general, pyrethrum flowers c ~ n only be gmwn on a commercial scale a t high altitudes near the equator. 8ucb countries M Ken-, BeJgipo Congo, and Braail are toaay among tbe world's leading wppliers. To reach American marketa, pyrethrum Bowers must be t r a n s
INDUSTRIAL A N D ENGINEERING CHEMISTRY
Vd. 46. No. 3
PLANT PROCESSES-Allethrin ported over vast distances, a factor which not only adds to their cost but which ordinarily renders the pyrethrum supply extremely uncertain in time of war. Subject to the vagaries of weather and to numerous other factors, pyrethrum lacks the basic dependability essential to the continued increasing use of a major insecticide. Efforts Made to Develop Synthetic Insecticide Having Same Desirable Properties as Pyrethrum
For many years, these problems, clearly reflected in the wide swings in the price of pyrethrum, gave increasing impetus to the search for new compounds equally as effective in killing insects and, a t the same time, just as harmless to man and animals. What was needed was an entirely synthetic insecticide that could be produced in the Cnited States in unlimited quantities from freely available raw materials. As one method of attack, researchers attempted to determine the exact chemical components that render pyrethrum toxic to inserts. Actually, this work had been going on for years. In 1924, Staudinger and Ruzicka in Switzerland had made important contributions t o the field by determining the acid segments of two of pyrethrum's insecticidal components, pyrethrins I and I1 ( 2 6 ) . Furthermore, they made considerable progress in determining the pyrethrolone segments of pyrethrins I and 11. The full solution to this problem, however, required years of additional work, mainly by LaForge and coworkers a t the Department of Agriculture. In the course of their studies, LaForge and collaborators discovered two additional active principles of the insecticide, namely cinerins I and 11. Then in 1947, LaForge and coworkers reached one of their major goals by achieving the final determination of the structures of pyrethrins I and I1 and cinerins I and I1 (16).
CH,
CH.
\C/
'
CHa
C=CH
/
CH3
I
'
C
/ \ CCHZCH=CHCH=CH* I 1
6'.
H-CHCOOCH
improved synthesis of chrysanthemum monocarboxylic acid ( 1), an important intermediate in the synthesis of cinerin I. The remaining problem was t o prepare the ketoalcoholic segment of the molecule (do). After months of work, Schechter, LaForge, and Green developed a general synthesis of cyclopentenolones (21, d5), which removed the last barrier to the preparation of cinerin I. Having accomplished this, the USDA chemists began testing a wide variety of compounds related to cinerin I, in an effort to dimover a compound possessing posFibly even greater insecticidal value than cinerin I itself. Of the compounds tested, the most potent and also the most suitable for commercial development was the allyl homolog of cinerin I, or allethrin (16).
CHI CH, \\ , /
CHI I
/ \
/ \
c
C
\
C=CHCH-CHCOOCH
CCH&H=CHz
I
/
I
CH, -C=O
CHa
Allethrin The Government's extensive research program on this insecticide led to a number of basic allethrin patents (%-%$), which are available for the free use of all persons in the United States. Since the Government had no interest in the foreign development of allethrin, U. S.Industrial Chemicals Co. early in 1950 acquired all foreign rights to these patents ( 3 ) . Although no licenses have yet been granted for the production of allethrin abroad, several are in the process of negotiation. hIanufacture in one or more foreign countries is a possibility in 1955. The name "allethrin," which waR adopted by the Department of ilgriculture's Interdepartmental Committee on Pest Control early in 1950, was announced in March of that year a t a meeting a t Boyce Thompson Institute in Yonkers, N. Y . ( 1 7 ) . At the same meeting, Carbide and Carbon Chemicals Co. reported the first commercial synthesis of allethrin, which up until that time had been known as allyl cinerin in this country and as allylrethrin in England.
CHs -C=O
CH,
Allethrin, a n Oily liquid, Consists of a Mixture of Eight Optically Active Isomers
Pyrethrin I
CH, CH,
CH,
I
'/ /\
CHaOCO
\
C
/ \
C=CHCII-CIICOOCII
4,
CCH2CH==CHCH=CH*
CH,-&=O Pyrethrin I1
CH"
CH3 CH
I
\ /
c
CH,
/ \
\
C=CHCH-CHCOO
/
dC\ H CCH,CH=CHCH3 1
Table I.
CH'--C=O
CHa
CHrOCO
CH,
\
I
\/ c / \
C
/\
C=CHCH -CHCOOCH
/
CH3
I
15 (max.) 1.005-1.015
1.5040 1.5010-1.6035
Less than 3% Mild, aromatic Ler-s than 0 . 1 %
CCH&H=CHCHa
1
CH,-C=O Cineiin I1
Early in 1948, research a t the USDA laboratory was directed toward the total synthesis of cinerin I, mainly because this compound, of all the four active materials isolated from pyrethrum, is the simplest chemically and the most stable. By then, Campbell and Hayper in England had already announced an
March 1954
Physical Properties of Commercial Allethrin (17)
Color on Gardner scale Specific gravity a t 20°/200 C. Refractive index a t 20' C. Refractive index a t 30' C. Aciditv calculated as chrvaanthemum monocarboxylic acid Odor Freon insolubles
Cinerin I CHj CH,
Since both cis and trans forms of d- and l-chryranthemum monocarboxylic acid are esterified with both d- and l-allethrolone in the synthesis of allethrin, the insecticide consists of a mixture of eight optically active isomers (19). Each of these isomers has its characteristic insecticidal properties. Commercial allethrin is an oily liquid that varies in color from pale yellow to reddish brown depending on the concentration of impurities. Some of the physical properties of allethrin are indicated in Table I.
Allethrin is used primarily in household and military aerosols and sprays for the control of flies and mosquitoes (8). Like pyrethrum, allethrin has the advantage both of quick knockdown and nontoxicity to humans and animals. Moreover, it has been found effective against insects resistant to D D T and other chlorinated insecticides. The official acceptance of allethrin for use in gas-propelled aerosols was announced by the Department of Agriculture in
INDUSTRIAL AND ENGINEERING CHEMISTRY
415
ENGINEERING, DESIGN, AND PROCESS DEVELOPMENT
;- all our insecticidal needs. This is xrue of alleshrin, as we!l as of all t’he otherj. EIomver, allethrin does have a ver iioiitoxic iimecticide field expaiidiiig program for
As far as the future market for allethrin is concerned, the exact extent of this demand has been the subject of widely varying estimates. One prediction, for example, is somewhere in the neighborhood of 200,000 pouiids a year. Much, of course. will depend on the future price of allethrin, as d l as on government policies regarding chemical residues in foodP. Much will also depend on the success of devclopmental programs noJy in progress. As part of this developniental woib, continued efiorts are being made t,o devise new or rspanded w e b for allethiin. Xllethrirr is being tested for a.pplication to a wide raiige of farm crop?, particularly near harvest. dl the same time, tlie use of allethrin in insect-resistant packaging materials for cereals and other food products is being actively explored. One maiiufact,urer is investigating the use of allethrin in livestock sprays containing the propylene glycol; which not only repells an alletlirin synergist. ng reearch program, allethrin is being critically compared with other insecticides. I n cornparkon t o DDT, for example, allethriii shows superioi Iriiuckdon-n against houseflies. In compari5on t o natural pyrethrum, allethrin gives virtually the same itnockdonn-approx~niately 947, in the standard Pee:-Grad? biological activity test (4j. Allethrin is also the equal of pyrethuni in killing power. This essentially equal effectiveness of allethrin mid pyrethrum against liouzefliec applies only, houever, \
