Potential insect control compounds which are chromenes, as well as their method of preparation and use, are disclosed. Compounds have been found which are effective in the control of insects by inhibiting the actions of juvenile hormone. Examples of useful compounds are 6,7-dimethoxy-2,2-dimethyl-3-chromene and 7-methoxy-2,2-dimethyl-3-chromene which can be extracted from the common bedding plant Ageratum houstonianum. Such compounds act to induce precocious maturation of immature insects, resulting in death either during or within a short time before or after the molting process. Additional effects which have been obtained include sterilization of mature insects, interruption of embryogenesis in insect eggs, the induction of diapause in insects and the prevention of sex pheromone secretion in insects.

BACKGROUND AND SUMMARY OF THE INVENTION 
The present invention is directed to compounds potentially useful in 
controlling insects. More particularly, the present invention is directed 
to active chromene compounds which are effective in inhibiting the effects 
of juvenile hormone in insects. 
Of the various chemical compounds which have been employed in the prior art 
as insecticides for controlling insects, many of such prior art compounds 
have also been found to be harmful to humans and other animal life. In 
addition, many species of insect pests have developed a resistance and 
even immunity to available insecticides. 
Alternative prior art methods for controlling insects have included the use 
of hormones, which interfere with the development of insects. Although 
such hormones have the advantage of apparently being harmless to other 
animals, their use is generally limited to application relatively late in 
the insect life cycle, after the insect has already produced its 
undesirable pest effect. 
The endocrine systems of insects secrete a certain hormone known as 
juvenile hormone which functions to control the biological activities of 
metamorphosis, reproduction, diapause and sex attractant production. In 
particular, juvenile hormone functions initially to maintain the young 
developing insect in an immature condition until it has developed to the 
point where it is ready to molt to the adult form. When maturation of the 
insect begins, the body ceases to secrete juvenile hormone until after the 
insect has passed into the adult form, at which time secretion of juvenile 
hormone recommences in order to promote the development of the sex organs. 
The forms in which juvenile hormone are known to occur in nature are 
discussed in the following publications: Trautmann et al., Z. Naturforsch, 
29C 161-168 (1974); Judy et al., Proc. Nat. Acad. Sci. USA, 70, 1509-1513 
(1973); Roller et al., Angew. Chem. Int. Ed. Eng., 6, 179-180 (1967); 
Meyer et al., Proc. Nat. Acad. Sci. USA, 60, 853-860 (1968); Judy et al., 
Life Sci., 13, 1511-1516 (1973); Jennings et al., Life Sci., 16, 1033-1040 
(1975); and Judy et al., Life Sci., 16, 1059-1066 (1975). 
In accordance with the present invention, it has been discovered that the 
lipid extract of the common bedding plant, Ageratum, contains two active 
compounds: (1) 6,7-dimethoxy-2,2-dimethyl-3-chromene; and (2) 
7-methoxy-2,2-dimethyl-3-chromene; each of which is effective to inhibit 
the effects of juvenile hormone in insects. Both compounds have been 
described in the literature: A. R. Alertsen "Ageratochromene, a 
Heterocyclic Compound from the Essential Oils of some Agertaum Species", 
Acta Chem. Scand. 9 (1955) No. 10, pp. 1725-1726; R. Huls "Syntheses De 
Chromenes Substitutes", Bull. Soc. Chim. Belg., 67 (1958), pp. 22-32; R. 
Livingston et al., J. Chem. Soc., p. 1509 et seq. (1957); and T. R. 
Kasturi et al., Tetrahedron Lett. 27 (1967), p. 2573 et seq. 
These and related chromene compounds inhibit the effects of Juvenile 
hormone, during early development of the insect and after reaching 
adulthood when the sex organs are undergoing development. By so inhibiting 
the effects of juvenile hormone, the maturing insect which has been 
treated with the present compounds is caused to die within a short time of 
such treatment. In addition, the ability of a treated insect to reproduce 
is prevented. The compounds of the present invention have also been found 
to interrupt embryogenesis in insect eggs, to induce diapause in insects 
and to prevent sex pheromone secretion in insects. The present compounds 
may be applied by suitable means including topically, orally or in a vapor 
state as a fumigant. 
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Based upon the activity of the extracts of Ageratum, compounds potentially 
suitable for use as anti-juvenile hormones are selected from those with 
the following general structure of Formula I. 
##STR1## 
wherein: R and R.sub.1 are H, lower alkyl, straight or branched chain, of 
about 1 to 4 carbon atoms, lower alkoxy, straight or branched chain, of 
about 1 to 3 carbon atoms, Cl, Br or F; 
R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are H, lower alkyl, straight or 
branched chain, of 1 to 6 carbon atoms, lower alkoxy, straight or branched 
chain, of 1 to 6 carbon atoms, OH, --OCH.sub.2 OCH.sub.3, --OC.sub.2 
H.sub.4 OC.sub.2 H.sub.5, --CO--OCH.sub.3, --CO--OCH.sub.2 CH.sub.3, 
##STR2## 
Cl, Br, F, --SCH.sub.3, --SCH.sub.2 CH.sub.3, --SCH.sub.2 CH.sub.2 
CH.sub.3, --NO.sub.2, or the structure wherein R.sub.2 and R.sub.3, or 
R.sub.3 and R.sub.4, or R.sub.4 and R.sub.5 are joined with a --OCH.sub.2 
O-- (methylenedioxy) group; or --OCH.sub.2 CH.sub.2 -(ethylenedioxy) group 
and 
Y is O, S or NH. 
The present invention also relates to a process for the manufacture of 
compounds of the above formula, which process comprises reacting a 
compound of the general Formula II: 
##STR3## 
wherein W is OH, SH or NH.sub.2 and R.sub.2, R.sub.3, R.sub.4 and R.sub.5 
are substituents given in FIG. I, with a compound of the general Formula 
III: 
##STR4## 
wherein, in Formula III: X is H, OH, Cl, Br or I; and 
R and R.sub.1 are as given in connection with Formula I; in the presence of 
a Friedel-Crafts catalyst such as formic acid, AlCl.sub.3, ZnCl.sub.2, 
polyphosphoric acid, SnCl.sub.4 or other similar catalyst well known in 
the art. A suitable solvent which is compatible with the Friedel-Crafts 
catalyst may be employed as necessary. Such a solvent may be, for example, 
ether, nitrobenzene or carbon disulfide. The reaction produces a 
chromanone of the general Formula IV: 
##STR5## 
wherein the substituents are those given with regard to Formula I. The 
addition of heat, by means such as conducting the reaction on a steam bath 
for one to several hours, may be employed although such heating is not 
always necessary for obtaining the chromanone product. 
The compounds of Formula IV are reduced with a reducing agent which may be 
any of those well known to one skilled in the art, such as lithium 
aluminum hydride or sodium borohydride, in a suitable solvent such as 
tetrahydrofuran or ether, to give a chromanol of the general Formula V: 
##STR6## 
wherein the substituents are those given in connection with Formula I. If, 
following reduction, the reaction mixture containing the compounds of 
Formula V are treated with a dilute acid such as hydrochloric, 
toluenesulfonic or other similar acid well known to those skilled in the 
art, dehydration of the hydroxyl group occurs giving the chromenes 
directly corresponding to the compounds given in connection with Formula 
I. When the chromanols are isolated directly, subsequent treatment with a 
catalytic amount of acid such as toluenesulfonic in refluxing benzene 
causes dehydration to the chromene. 
In the case of the reaction of the compounds of general Formula II with 
unsaturated aldehydes of Formula III in the presence of Friedel-Crafts 
catalysts, the desired chromenes are produced directly. 
In alternative procedures, a compound having the structure of Formula II is 
reacted with one of the following: 
##STR7## 
where R and R.sub.1 have the meaning specified above and X' is a halogen 
or hydroxyl group. The chroman resulting from this reaction is then 
dehydrogenated by conventional techniques to give the corresponding 
chromene. 
Preliminary screening of the compounds in addition to the Ageratum extracts 
indicates that the nucleus: 
##STR8## 
where n is from about 1 to 6, is important for activity. The nucleus may 
be modified in accordance with well known principles of molecular 
manipulation to produce compounds for screening. In particular the path 
followed for the synthesis of juvenile hormones and their analogs and 
homologs combined with the known techniques for producing insecticides 
suggests a useful approach to molecular modification. 
A preferred method of this invention comprises contacting an insect with an 
anti-juvenile hormone selected from active compounds having the structure: 
##STR9## 
wherein R is methyl, R.sub.1 is methyl or ethyl, R.sub.3 is methoxy, 
ethoxy or H and R.sub.4 is methoxy, ethoxy or propoxy, in an amount and 
concentration sufficient to alter the development of said insect. 
Alternatively R.sub.4 may be methoxymethoxy or ethoxyethoxy. 
A further embodiment of this invention comprises contacting an insect with 
an anti-juvenile hormone selected from active compounds which are dipyran 
benzenes having the substituents referred to above. In particular, the 1,7 
and 1,9 dipyran benzenes, such as the following compounds, are useful: 
6-methoxy-2,2,8,8, tetramethyl-1,7-dipyran benzene 
##STR10## 
2,2,8,8-tetramethyl-1,7-dipyran benzene 
##STR11## 
2,2,8,8-tetramethyl-1,9-dipyran benzene 
##STR12## 
The following specific examples further illustrate the preparation of 
compounds within the scope of the general structures shown above.

EXAMPLE 1 
Synthesis of 6,7-dimethoxy-2,2-dimethyl-3-chromene 
The amount of 10 g of 3,4-dimethoxyphenol and 7.8 g of 3,3-dimethyl acrylic 
acid were combined in a 125 ml. erlenmeyer flask and dissolved with the 
addition of 40 ml anhydrous ethyl ether. The ether was removed in vacuo 
and while the contents of the flask remained liquid, 50 gm of 
polyphosphoric acid was added. The flask and contents were placed on a 
steam bath and heated with stirring for 1 hour. At the end of 1 hour, 75 
ml. of water was added and the contents stirred into solution for 5 
minutes. The solution was allowed to cool and a substantial sticky 
precipitate formed. The aqueous layer was decanted and extracted with 100 
ml. of ether. The ether extract was washed successively with 150 ml. of 
water, 100 ml. of 5% sodium carbonate and 100 ml. of saturated NaCl 
solution. The ether extract was dried over anhydrous sodium sulfate. The 
sticky residue formed on cooling was dissolved in 300 ml. of chloroform 
and washed successively with 150 ml. of water, two 150 ml. portions of 5% 
sodium carbonate solution and 150 ml. of saturated NaCl solution. The 
chloroform solution was dried over anhydrous sodium sulfate. The ethereal 
and chloroform extracts were combined and the solvents removed in vacuo 
leaving 16.17 gm of off-white crystalline chromanone. 
The chromanone was dissolved in 400 ml. of dry ethyl ether, and 2.5 gm of 
lithium aluminum hydride was added in portions. The reaction was refluxed 
for 2 hours and then allowed to come to room temperature. The excess 
lithium aluminum hydride was destroyed by dropwise addition of water and 
150 ml. of 4N HCl was added slowly to the reaction mixture. Stirring was 
continued for 15 minutes. The reaction mixture was extracted with ether 
and washed successively with 100 ml. of water, 100 ml. 5% sodium carbonate 
solution and 100 ml. saturated NaCl solution. The ethereal extract was 
dried over anhydrous sodium sulfate. Removal of the ether in vacuo gave 
15.6 g of crude chromene. 
Distillation at 4 mm gave 10 gm of pure 
6,7-dimethoxy-2,2-dimethyl-3-chromene BP 142.degree.-144.degree. C. The 
residue remaining after distillation was chromatographed over Florisil, 
trade name of a magnesium silicate adsorbent, and eluted with increasing 
concentrations of ether in petroleum ether to yield 2.2 g of additional 
pure chromene. The combined yield was 12.2 gm or a total yield of 79% of 
the theoretical. Purity was determined to be greater than 99% by 
thin-layer and gas-liquid chromatography. The structure was verified by 
infra-red and nuclear magnetic resonance spectroscopy. 
An alternate synthesis involves the reaction of an appropriate phenol with 
3-methyl-2-butene-1-ol or 3-methyl-1-bromo-2-butene or 
3-methyl-1-butene-3-ol in the presence of a catalyst such as formic, 85% 
polyphosphoric acid, acetic acid or ZnCl.sub.2 to produce the 
corresponding chromane. The chromane is treated with a dehydrogenating 
agent such as chloranil or DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) 
in a suitable solvent such as benzene or xylene to introduce the double 
bond and give the corresponding chromene. 
EXAMPLE 2 
Synthesis of 6,7-methylenedioxy-2,2-dimethyl chromene 
5.1 gm of 3-methyl-1-bromo-2-butene was combined with 4 gm of 
3,4-methylenedioxyphenol and dissolved in 50 ml. of pentane and 50 ml. 
benzene. 2 gm of anhydrous ZnCl.sub.2 was added and the reaction mixture 
refluxed for 1 hour and cooled. The mixture was extracted with ether and 
washed successively with 100 ml. of water, 100 ml. 5% sodium carbonate and 
100 ml. of saturated salt solution. After drying the extract over 
anhydrous sodium sulfate, the solvent was removed in vacuo leaving 7.4 g 
of crude chromane. The crude material was fractionated on a column of 
Florisil and eluted with increasing concentrations of ether in petroleum 
ether to yield 4.5 g of pure chromane. 
One gram of the chromane was dissolved in 75 ml. of benzene and 1.2 g of 
DDQ added. The reaction mixture was refluxed for 4 hours, then cooled and 
filtered. Removal of the solvent from the filtrate gave 1.35 g of crude 
product. Chromatography over Florisil gave 0.95 gm of pure 
6,7-methylenedioxy-2,2-dimethyl-3-chromene. Structure and purity were 
determined by thin-layer and gas-liquid chromatography and NMR 
spectroscopy. 
EXAMPLE 3 
Synthesis of 6,7-dimethoxy-2-methyl-2-ethyl chromene 
A complementary synthesis similar to the above involves reaction of an 
appropriate phenol with an allylic alcohol in the presence of formic acid 
to yield the chromane in high yield. This followed by dehydrogenation with 
chloronil or DDQ, gives the desired chromene. 
Thus, 2 g of 3,4-dimethoxy phenol and 1.9 g of 3-methyl-1-pentene-3-ol were 
combined in 10 ml. formic acid with stirring at room temperature for 18 
hours. Formic acid was removed in vacuo. The residue dissolved in ether 
was washed successively with 100 ml. of water, 100 ml. 5% sodium carbonate 
and 100 ml. saturated salt solution. The ether solution was dried over 
anhydrous sodium sulfate and gave 3.5 gm of crude product on removal of 
the ether in vacuo. Chromatography over Florisil gave 2.5 g of pure 
chromane. The amount of 0.88 gm of the pure chromane was dissolved in 100 
ml. benzene and refluxed for 1 hour with 0.95 g DDQ. After cooling, 
filtration, and removal of the solvent, the filtrate gave 1.1 g crude 
product which on chromatography over Florisil gave 0.55 g of pure 
6,7-dimethoxy-2-methyl-2-ethyl chromene. Purity and structure were 
determined by thin-layer and gas-liquid chromatography and by NRM 
spectroscopy. 
EXAMPLE 4 
Synthesis of 6,7-dimethoxy chromene 
The synthesis of chromenes which are unsubstituted in the 2-position was 
accomplished by reaction of the appropriate phenol with acrylonitrile 
under basic catalysis to give the phenoxy-propionitrile which was 
converted to the corresponding phenoxy-propionate by treatment with acid. 
Ring closure to the chromanone was effected by treatment with 
polyphosphoric acid and the chromene obtained by reduction of the 
chromanone with any of several reagents such as lithium aluminum hydride 
or sodium borohydride followed by treatment with acid to promote 
dehydration to the chromene. 
Thus 5 gm of 3,4-dimethoxyphenol; 6.88 g acrylonitrile and 0.5 ml. of 
Triton B, trade name of N-Benzyltrimethylammonium hydroxide, (40% soln.), 
were combined and refluxed for 18 hours. After cooling the reaction 
mixture was extracted with chloroform and washed with 5% sodium hydroxide, 
and with saturated salt solution. The organic layer after drying over 
anhydrous sodium sulfate gave 4.4 gm of 3,4-dimethoxy phenoxy 
propionitrile on removal of the solvent. The amount of 2.2 g of the 
nitrile was combined with 40 ml. of water and 80 ml. of concentrated 
hydrochloric acid and refluxed for 2 hours. The reaction mixture on 
cooling was extracted with ether and washed with water and 5% sodium 
hydroxide. The basic wash was acidified with 6N hydrochloric acid and 
extracted twice with ether. The ethereal extract was washed twice with 
water and with saturated salt solution. Drying over anhydrous sodium 
sulfate and removal of the solvent in vacuo gave 1.25 g of the crude 
3,4-dimethoxy phenoxy propionic acid. The crude product was combined with 
5 gm of polyphosphoric acid and heated at 75.degree.-85.degree. C. for 1 
hour. The reaction mixture was extracted with ether and washed with 10% 
sodium carbonate solution and saturated salt solution. Drying over 
anhydrous sodium carbonate and removal of the solvent gave 0.35 gm of pure 
6,7-dimethoxy chromanone. The chromanone was dissolved in 50 ml. dry ether 
and refluxed 1 hour with an excess of lithium aluminum hydride. On 
cooling, the reaction was stopped by addition of 10 ml. of water and then 
stirred for 15 minutes with 10 ml. of 2N hydrochloric acid. The reaction 
mixture was extracted with ether and washed with water and saturated salt 
solution to give on drying and removal of the solvent 0.31 gm of pure 
6,7-dimethoxy chromene. 
EXAMPLE 5 
The following Table I provides a flow chart showing the isolation of the 
two natural products from Ageratum, including the column fractionation and 
thin-layer chromatography. 
TABLE I 
__________________________________________________________________________ 
AGERATUM HOUSTONIANUM 
__________________________________________________________________________ 
##STR13## 
##STR14## 
Compound 1 
NMR (100 MHz, CCl.sub.4), 1.38 (6H,s), 
3.69 (3H,s), 5.31 (1H,d,J=10) 6.13 
(1H,d,J=10), 6.18 (1H,s), 6.21 
(1H,d,J=9), 6.70 (1H,d,J=9) 
Compound 2 
NMR (100 MHz, CCl.sub.4), 1.37 (6H,s), 
3.69 (3H,s), 3.74 (3H,s) 5.52 (1H,d,J=10), 
6.11 (1H,d,J=10), 6.24 (1H,s), 6.39 
(1H,s) 
__________________________________________________________________________ 
INDUCTION OF PRECOCIOUS DEVELOPMENT 
In accordance with the present invention, active chromenes were found to 
cause precocious maturation when applied to an immature insect. The 
juvenile hormone (JH) is a natural insect hormone which acts to keep the 
developing insect immature until it is ready to molt to the adult form. 
When maturation of the insect begins, the insect ceases to produce JH and 
the insect matures to the adult form. The compounds of the present 
invention have been found to stop the action of JH and cause the immature 
insect to begin the maturation process. For some insects the induced lack 
of JH causes such rapid maturation that the immature insect dies shortly 
prior to, or during the molting process. In other insects the lack of JH 
causes them to molt into miniature adults which completely avoids the 
tremendous feeding potential of the immature stages and results in tiny 
adults which are sterile, very fragile and which die soon after molting. 
The anti-juvenile hormone action can be overcome by the application of 
exogenous juvenile hormone, which indicates that the anti-juvenile hormone 
compounds act by interfering with the synthesis of juvenile hormones. 
Tables II and III illustrate the induction of precocious maturation by 
contacting the milkweed bug with a chromene in accordance with the present 
invention. Other Hemiptera are also quite sensitive, and precocious 
metamorphesis has been induced in Lygaeus kalmii Stal and in Dysdercus 
cingulatus. Satisfactory results have not been obtained in inducing 
precocious metamorphesis in Holometabola. 
TABLE II 
______________________________________ 
Induction of Precocious Maturation 
in the Milkweed Bug by Lipid Extract 
of Ageratum 
Crude Lipid Extract of 
Ageratum.sup.(1) Concentration 
Precocious 
.mu.g/cm.sup.2 Adults %.sup.(2) 
______________________________________ 
15 100 
7 80 
4 27.8 
2 0 
control 0 
______________________________________ 
.sup.(1) Ether-acetone (11) extract of macerated plant tissue. 
.sup.(2) Twenty 2nd instar nymphs were continuously exposed to the extrac 
residue spread over a 9 cm petri dish containing milkweed seeds and water 
Insects molted to apparently normal 3rd and 4th instar nymphs and then 
molted precociously to adult insects. 
At high concentrations a minor percentage of the treated nymphs are unable 
to molt and remain as nymphs until death. 
TABLE III 
______________________________________ 
Induction of Precocious Maturation 
in the Milkweed Bug by Pure Ageratochromene 
Ageratochromene.sup.(1) 
Precocious 
.mu.g/cm.sup.2 Adults %.sup.(2) 
______________________________________ 
0.7 90 
0.4 15 
control 0.0 
______________________________________ 
.sup.(1) Pure synthetic ageratochromene 
(6,7dimethoxy-2,2-dimethyl-3-chromene). Twenty 2nd instar nymphs were 
confined in a 9 cm petri dish with the synthetic antiJH compound prepared 
in accordance with the present invention. 
.sup.(2) Insects molted to 3rd and 4th instars and then molted into 
precocious adults. 
STERILIZATION 
In the normal adult insect, JH (or gonadotropic hormone) is produced again 
after molting to the adult form and is then necessary for the development 
of the insect ovaries. Treatment of adult insects with 
6,7-dimethoxy-2,2-dimethyl-3-chromene as described below in Table IV was 
found to prevent or stop the action of JH and the insect ovaries failed to 
develop. If the insect ovaries were developed at the time of treatment, 
they rapidly regressed to the undeveloped state. In either event, 
reproduction was prevented. This technique has been successful with 
insects in the orders Hemiptera, Diptera and Coleoptera. 
TABLE IV 
______________________________________ 
Sterilization of Insects With 
Anti-Juvenile Hormone 
Concentrations of synthetic 
Ageratochromene which 
prevented ovary development 
Insect 
______________________________________ 
7.0 .mu.g/cm.sup.2(1) 
Adult Milkweed Bug 
( Oncopeltus fasciatus) 
7.0 .mu.g/cm.sup.2(2) 
Cotton Stainer 
( Dsydercus intermedius) 
1.5 .mu.g/cm.sup.2(3) 
Apple Maggot 
( Rhagoletis pomonella) 
1000 ppm spray.sup.(4) 
Mexican Bean Beetle 
( Epilachna varivestis) 
______________________________________ 
.sup.(1) Eight newly emerged adults confined to treated 9 cm petri dish 
for 48 hours. Ovaries examined for development after 6 days. 
.sup.(2) Ten newly emerged adults confined to treated 9 cm petri dish for 
72 hours. Ovaries examined for development after 13 days. 
.sup.(3) Forty-five newly merged apple maggot females were confined to a 
cm petri dish containing a residue of the test compound for 30 hours. 
After treatment flies were held in oviposition cages and examined for 
ovarian development when control insects began oviposition. 
.sup.(4) Ten newly emerged Mexican Bean Beetle females were sprayed while 
feeding on a bean plant with emulsified ageratochromene. Ovaries were 
dissected out and examined for development when controls began 
oviposition. 
SEX PHEROMONE INHIBITION 
The method of this invention is also useful to inhibit sex pheromone 
production. Pheromone producing virgin female cockroaches (Periplaneta 
americana L.) were treated topically with 
6,7-dimethoxy-2,2-dimethyl-3-chromene in the manner used to induce 
diapause (see Table VII below). This leads to the termination of sex 
attractant secretion within five days whereas untreated control 
cockroaches continued to produce pheromone for at least fifteen days. 
OVICIDAL ACTIVITY 
The control of embryogenesis in the insect egg by juvenile hormone is 
poorly understood. However, molting is known to occur in certain insect 
eggs and juvenile hormones have been extracted from insect eggs, implying 
a presumptive role of JH during embryogenesis. As shown in Table V and VI 
below, 6,7-dimethoxy-2,2-dimethyl-3-chromene was found to demonstrate 
ovicidal activity by contact and by fumigation, presumably by interfering 
with JH production by the insect embryo. 
TABLE V 
______________________________________ 
Ovicidal Activity of Anti-Juvenile Hormone 
Compound by Contact Spray on Mexican Bean Beetle Eggs 
Concentration of Synthetic 
% % Dead 
Ageratochromene in Spray.sup.(1) 
Hatch Nymphs 
______________________________________ 
100 ppm 2.7 100 
10 ppm 18.4 76.7 
control 80.0 0.0 
______________________________________ 
.sup.(1) Four day old eggs on bean leaves were sprayed with 
Ageratochromene in emulsion formulation. 
TABLE VI 
______________________________________ 
Ovicidal Activity of Anti-Juvenile 
Hormone Compound by Fumigation 
Concentration (mg) Synthetic 
Ageratochromene Which 
Prevented Egg Hatch or Survival 
of 1st Instar Insects.sup.(1) 
Insect 
______________________________________ 
0.5 mg Milkweed Bug 
0.2 mg Mexican Bean Beetle 
______________________________________ 
.sup.(1) Newly laid eggs were confined in watch glasses exposed to vapors 
of compound placed on lid of watch glass. A small percentage of nymphs or 
larvae sometimes emerged from the eggs but died within a few hours. 
DIAPAUSE INDUCTION 
Many insects enter a state known as diapause in order to survive inclement 
climatic conditions such as winter, hot dry summers, etc. During diapause 
insects do not feed, mate or reproduce. Diapause occurs in many insects 
when the production of JH ceases. As shown in Table VII below, 
6,7-dimethoxy-2,2-dimethyl-3-chromene was found to stop the action of JH 
when applied topically and to cause the insect to go into diapause. 
Insects in diapause stop feeding, thus are enable to cause crop damage and 
if diapause is prolonged, the insects become weak and die. The induction 
of diapause with these anti-JH chemicals thus becomes a very unique method 
of insect control. 
TABLE VII 
______________________________________ 
Induction of Diapause in 
Adult Colorado Potato Beetles 
Synthetic 
Ageratochromene 
Insects Entering 
Topical (.mu.g).sup.(1) 
Diapause %.sup.(2) 
______________________________________ 
500 40 
250 38 
100 75 
control 0 
______________________________________ 
.sup.(1) Insects were treated topically on the abdomen with the 
antijuvenile hormone in 1 .mu.l of acetone and placed upon potato plants 
growing in soil. 
.sup.(2) After 21 days insects remaining on the potato plants were judged 
nondiapausing. Insects which had entered the soil and become quiescent 
were screened from the soil and judged to be diapausing. 
FURTHER SCREENING 
Preliminary screening indicates that numerous chromenes having the formula 
or the nucleus: 
##STR15## 
where R is methyl, R.sub.1 is methyl or ethyl and n is 1 to 6, or 
preferably n is 1 to 3, induce precocious maturation. The tables below set 
forth numerous useful compounds against the milkweed bug and provide a 
basis for further molecular modification to produce chromenes for the 
present invention. 
TABLE VIII 
______________________________________ 
Induction of Precocious Maturation 
and Sterilization of Milkweed Bug 
by Anti-Juvenile Hormone Compounds 
Concentration 
(.mu.g/cm.sup.2)* (% 
Precocious 
Compound Adults) 
______________________________________ 
6,7-dimethoxy-2,2-dimethyl-3-chromene 
1.9 (100%) 
6,7-diethoxy-2,2-dimethyl-3-chromene 
1.9 (100%) 
6-ethoxy-7-methoxy-2,2-dimethyl-3-chromene 
1.9 (100%) 
6-methoxy-7-ethoxy-2,2-dimethyl-3-chromene 
.4 (100%) 
6-methoxy-7-isopropoxy-2,2-dimethyl-3-chromene 
.8 (100%) 
6-methoxy-7-propoxy-2,2-dimethyl-3-chromene 
3.9 (100%) 
6-methoxy-7-butoxy-2,2-dimethyl-3-chromene 
3.9 (50%) 
6-methoxy-7-hexoxy-2,2-dimethyl-3-chromene 
3.9 (15%) 
6,7-dimethoxy-2-methyl-2-ethyl-3-chromene 
3.9 (50%) 
7-ethoxy-2,2-dimethyl-3-chromene 
3.9 (100%) 
7-methoxy-2,2-dimethyl-3-chromene 
3.9 (60%) 
6-bromo-7-ethoxy-2,2-dimethyl-3-chromene 
3.9 (15%) 
______________________________________ 
*In the standard procedure, twenty 2nd instar nymphs were confined to 9 c 
petri dishes containing the antijuvenile hormone. Precocious adults were 
examined after 5 days for ovarian development and were determined to be 
sterile. 
Analogs of the foregoing compounds have also been found useful and are 
listed below. 
TABLE IX 
______________________________________ 
Concentra- 
tion (.mu.g/cm.sup.2) 
(% 
Precocious 
Adults) 
Milkweed 
Compound Bug 
______________________________________ 
##STR16## 3.9 (100%) 
7-ethoxyethoxy-2,2-dimethyl-3-chromene 
##STR17## 3.9 (limited activity) 
6,7-ethylenedioxy-2,2-dimethyl-3-chromene 
##STR18## 1.9 (20%) 
2,2,8,8-tetramethyl-1,9-dipyran benzene 
##STR19## 1.9 (45%) 
2,2,8,8-tetramethyl-1,7-dipyran benzene 
##STR20## 1.9 (100%) 
6-methoxy-2,2,8,8-tetramethyl-1,7-dipyran benzene 
______________________________________ 
Additional compounds have been preliminarily screened without satisfactory 
results in inducing precocious maturation in the milkweed bug but which 
have led to sterilization of the milkweed bug. These compounds are listed 
in Table X. 
TABLE X 
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6,7-dimethoxy-3-chromene 
6,7-dimethoxy-2-methyl-3-chromene 
7-methoxy-6-hydroxy-2,2-dimethyl-3-chromene 
7(3-propynyloxy)-2,2-dimethyl-3-chromene: 
##STR21## 
6,7-dimethoxy, 2,2-dimethyl-3,4-cycloprop-chroman: 
##STR22## 
6,7-dimethoxy, 2,2-dimethyl-3,4-cycloprop (dichloro)-chroman: 
##STR23## 
______________________________________ 
The remaining chromenes and their analogs which have been preliminarily 
tested have not provided satisfactory results. Similarly unsuccessful 
preliminary results have been obtained on certain insects other than those 
reported above. These results are not sufficiently definitive to determine 
whether such compounds lack any utility and more comprehensive testing 
appears necessary against various types of insects. However, the broad new 
approach to insect control evidenced by the foregoing data provides an 
impetus and a basis for further screening of chromenes, their analogs, and 
the techniques of application to optimize this invention. 
The screening procedure for determining anti-juvenile hormone activity is 
readily carried out by contacting an immature insect, preferably a 2nd 
instar nymph, with a compound to be tested in a concentration which can 
vary greatly. Either direct contact or contact with the insect's 
environment with from about 0.4 to 4 .mu.g/cm.sup.2 of the compound to be 
tested is a useful procedure. The insect is then observed to determine its 
mode of further development. A further screening technique is to test for 
sterilization, or other effects of anti-juvenile hormones, in the manner 
set forth in the above description and examples. By these techniques the 
potentially usefull compounds within the scope of Formula I and analogs of 
these compounds are readily screened to determine which are suited for 
different application conditions and insects. 
This invention is further set forth in the publication "Discovery of Insect 
Anti-Juvenile Hormones in Plants" by Bowers et al., Science, Vol. 193, pp. 
542-547 (Aug. 13, 1976), incorporated herein by reference.