CA1086322A - 6,7 dialkoxy-2,2-dialkyl-3-chromene compounds - Google Patents

Abstract

ANTI-JUVENILE HORMONES
ABSTRACT OF THE DISCLOSURE
Insect control compounds as well as their method of preparation and use are disclosed. The compounds are chromenes. Such compounds have been found to be effective in control of insects by inhibiting the actions of juvenile hormone. Thus the present compounds act to induce pre-cocious 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 ob-tained 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.

Description

BACKGROUND AND SUMMARY OF THE INVENTION
The present invention is directed to compounds for use in controlling insects. More particularly, the present invention is directed to chromene compounds which have been found to be 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 l~fe. In addition, many species of insect pests have developed a resistance and even immunity to available insecticides.
Alternative prior art methods for controlling in-sects 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 - : . : :, ., ,, ~.:,, .;, . -: . . - . :

`~`` 1~8~i322 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 con-dition until is 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 juveni~e 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 ogans. `
The forms in which juvenile hormone are known to `~
occur in nature are discussed in the following publica-tions: 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.
., 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 ef- ;
fective to inhibit the effects of juvenile hormone in :

.

1~8~;322 insects. The first compound has been described by A.
R. Alertsen in the article "Ageratochromene, a ~Ieterocyclic Compound from the Essential Oils of some Ageratum Species"
in Acta Chem. Scand. 9 (1955) No. 10 p. 1725-1726.
Additional work in this area has been published by R. Huls in the article "Syntheses De Chromenes Substitues" in Bull. Soc. Chim. Belg., 67 (1958), pp. 22-32.
By the present invention, chromene compounds are provided which have been found to effectively inhibit the effects of juvenile hormone, both 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 ~-In accordance with the principles of the present invention, compounds suitable for use as anti-juvenile hormones have the following general structure:
'.,:

~

:~:
wherein: :~
R and Rl are H or an alkyl, straight or branched chain, of 1 to 4 carbon atoms;
R2 is hydrogen;
R3 is hydrogen or alkoxy of 1 to 6 carbon atoms; or -R4 is alkoxy of 1 to 6 carbon atoms R3 and R4 are joined with a -OCH2O- group and R5 is hydrogen. -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 I:
R :~

4 ~ w .

3 ~

2 :~ -wherein W is OH, and R2, R3, R4 and R5 are substituents given in Figure I, with a compound of the general formulae II: .

R R ~ ~
,.~ I I ,,~.. ..
Rl-C=CH-V or Rl-f-CH=CH2 OH

wherein, : V is -COOH, -CH2OH, -CH2Br or -C-N ~-R and Rl are as given in connection with Figure I;
:: in the presence of a Friedel-Crafts catalyst such as formic :
: acid, AlC13, ZnC12, polyphosphoric acid, Sn C14 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 ex- ::

. ~

" , , ,..... ~ . . . .

~08632Z

ample, ether, nitrobenzene or carbon disulfide. The reaction produces a chromanone of the general Formula III:
: R5 R
R4 ~ R

wherein the substituents are those given with -regard to Figure I. The addition of he.at, 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 pro-I duct.
1 The compounds of Formula III 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 IV: ~:

5 R ~;

4 ~ 1 R3 :~

wherein the substituents are those given in con- -nection with Figure I. If, following reduction the reaction mixture containing the compounds of Formula IV are treated with a dilute acid such as hydrochloric, toluenesulfonic : 30 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 Figure I. When the chromanols are isolate 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 compounds of general Formula I with unsaturated aldehydes of Formula II in the presence of Friedel-Crafts catalysts, the desired chromenes are produced directly.
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 con-tents 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 sol-~tion 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 offwhite 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 142-144C. 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 resonace spectroscopy.
An alternate synthesis involves the reaction of an appropriate phenol with 3-methyl-2-butene-1-ol or : .. , . . . .. ... .. . . . . ~

1()86322

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 ZnC12 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 corres-ponding chromene.

Example 2 Synthesis of 6, 7-methylenedioxy-2, 2-dimethyl chromene. 5.1 gm of 3-methyl-1-bromo-2-butene was com-bined with 4 gm of 3, 4-methylenedioxyphenol and dissolved in 50 ml pentane and 50 ml benzene. 2 gm of anhydrous Zn~12 was added and the reaction mix-ture refluxed for 1 hour and cooled. The mixture was extracted with ether and washed successively with 100 ml of water, 100 ml 5% sodium car-bonate 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 chromene. Structure and purity were determined by thin-layer and gas-liquid chroma-tography and NMR spectroscopy.

1~6322 Example 3 A complimentary 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 ~ - 3 with chloronil or DDQ, gives the desired chromene.
Thus were combined 2 g of 3, 4-dimethoxy phenol and 1.9 g of 3-methyl-1-pentene-3-ol 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 MNR spectroscopy.
Example 4 The synthesis of chromenes which are unsubstituted in the 2-position was accomplished by reaction of the approriate 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 : _ g _ ' ~86322 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 acrylo-nitrile and 0.5 ml of Triton B, trade name of N-Benzyl-trimethylammonium 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 con-centrated 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 6 N hydrochloric acid and ex- ~;
i tracted 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, 5-dimethoxy phenoxy propionic acid. The crude product was combined -`
with 5 gm of polyphosphoric acid and heated at 75-85C i . , , 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 dis-solved in 50 ml dry ether and refluxed 1 hour with an excess of lithium aluminum hydride. On cooling, the re-action was stopped by addition of 10 ml of water and then ~
.-. :

36:}ZZ

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 show-ing the isolation of the two natural products from Ageratum, including the column fractionation and thin-layer chromatography.

. ~
,'~' .
?i;
-- 11 -- , 10~632Z

U~ _ ~, ,, CO
:
o ~ ~ C~

~ , ~ ~ e . o\ ~ .
,~ , . ~ o ~ ~ -:- ~ji o ~~1 : h ~ ~! o ~
O ~ ) ~ o ~ 11 :
f~ ~ _ . . ~
E~ ~~ ~ ~ ~ .
. O . ~ 1:~1 ~ I E~ _ O ~ a) ~ . oP
~-1 O oo 3 ~
~ ~ J~ ~ ~ ~ O ~ -- ;' N _ ~ 0 3 o ~ I ~ .
D ~ p ,0 0 ~ ~ Iy ~ ~a ~ ~, O~) , O r~ ~ ~ Ll~ u~ O o t. u~

.a ~la ~ ,, ~ o IY . ~ ~ ~,) 7~
~ ~ ~ _ \ / ~
0~ ~ li:l ~ 1 P;
o Q, ~ ~ .
,¢ .~ 5~ o .~ ~ ~ ~ ~ m .
. ~ ~ ~ m ~ .~
o ~ ~ o O
~ s~ ~ a) ~ ~ m ,~ -~ ~ ~ ~ .~ .~ .~
dP t` ~ ` O
L~ e ~~
~ O C,) ~ ~
.~

e~ C~ 3 o ~ o U~
.~ O ~o :~ O ~ U \
~ ~ o~ ~ Z~ Z~ ~ , '' ~ ~ -~

O O ~
.~ \ O O
~ ~ 0~ 0 ' J 0~6:}Z2 Induction of Precocious Development In accordance with the present invention, the chromenes and substituted chromenes were synthesized and 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 J juvenile hormones.

.. . .
~ r .~

: ~ :

Induction of Precociuos Maturation in the Milkweed Bug ~y Lipid Extract of Ageratum :
Crude Lipid Extract of AgeratumlJConcentration Precocious ~g/cm2 Adults %~
' -:

7 80 ~ ~

4 27.8 ~-2 0 ` ~-~
Control 0 ~ ~ -Ether-acetone (1-1) extract of macrerated plant tissue.

Twenty 2nd instar nymphs were continuously exposed to the extract 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.
;'` '~ ~',:
.. .. ~': ~
~,i. . . .

:~. .

.. .

..
. . .
'''' . .

: ' 1~6322 Induction of Precocious Maturation in the Milkweed Bug by Pure Ageratochromene Ageratochromene~ Precocious ~g/cm Adults %~

0.7 90 -~
0.4 15 --control 0.0 ~, ~/Pure synthetic ageratochromene (6, 7-dimethoxy--~ 2, 2-dimethyl-3-chromene). Twenty 2nd instar nymphs were confined in a 9 cm petri dish with the synthetic anti-JH compound prepared in ac-cordance with the present invention.
~/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.
c Treatment of adult insects with the compounds of the present invention as desecribed hereinafter was found to prevent or ~ stop the action of JH and the insect ovaries fail 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.

'; ;:

~0863ZZ

Sterilization of Insects with Anti-Juyenile Hormone . .
Concentrations of synthetic ,~
Ageratochromene necessary to prevent ovary development Insect ~ .
7.0 ~g/cm2 ~ Adult Milkweed Bug (Oncopeltus fasciatus) 7.0 ~g/cm2 ~ Cotton Stainer (Dsydercus intermedius) 1.5 ~g/cm ~ Apple Maggot (Rhagoletis pomonella) 1000 ppm spray ~ Mexican Bean Beetle J (Epilachna varivestis) Eight newly emerged adults confined to treated 9 cm petri , dish for 48 hours. Ovaries examined for development after ;
., .
6 days. -- ~ Ten newly emerged adults confined to treated 9 cm petri dish for 72 hours. Ovaries examined for development after 13 days.
-^~ 20 ~ Forty-five newly emerged apple maggot females were con-f fined to a 9 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 devel-opment when control insects began oviposition.
Ten newly emerged Mexican Bean Beetle females were sprayed while feeding on a bean plant with emulsified agerato-~08632Z

chromene. Ovaries were dissected out and examined for development when controls began oviposition.

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. The compounds of the ~ -present invention were found to demonstrate ovicidal activity by contact and by fumigation, presumably by inter-fering with JH production by the insect embryo.

Ovicidal Activity of Anti-Juvenile Hormone Compound by Contact Spray on Mexican Bean Beetle Eggs i ~
Concentration of Synthetic % % Dead Ageratochromene in Spray~ Hatch Nymphs 100 ppm 2.7 100 ~i10 ppm 18.4 76.7 Control 80.0 0.0 -,,"~ ' ~

~`~ 20 ~ Four day old eggs on bean leaves were sprayed with ~¦ Ageratochromene in emulsion formulation. ~ -r i , 1(~86322 Ovicidal Activity of Anti-Juvenile Hormone Compound by Fumigation ~, Concentration (mg) Synthetic Ageratochromene Necessary to Prevent Egg Hatch or Survival of 1st Instar Insects ~ Insect 0.5 mg Milkweed Bug 0.2 mg Mexican Bean Beetle " ~

~J 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. ~ -,,., . :
,l 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 in-sects when the production of JH ceases. The compounds of ~ -the present invention were 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 unable to cause crop damage and if diapause is prolonged, the in-sects become weak and die. The induction of diapause with these anti-JH chemicals thus becomes a very unique method of insect control.
,,'~

108G:}ZZ

Induction of Diapause in Adult Colorado Potato Beetles Synthetic Ageratochromene Insects Entering Topical (~g) ~ Diapause ~-' : 100 75 Control 0 ~:
.~ .,'' ~ Insects were treated topically on the abdomen with the ;:, antijuvenile hormone in 1 ~1 of acetone and placed upon :
potato plants growing in soil.
2 After 21 days insects remaining on the potato plants were judged non-diapausing. Insects which had entered -, the soil and become quiescent were screened from the soil ~-~ ~ .
.~ and judged to be diapausing. ~ ~

~ ~ : -'~ .' ;.-.,~ , ,, . ~. ,.

, ":
.' , .

10863;Z2 Induction of Precocious Maturation and Sterilization of Milkweed Bug by ~nti-Juvenile Hormone Compounds Compound Concentration~ ~g/cm2 .

~ ~, o ~ll 4.0 ~0~
'7; -~ ~

~ 0~ 0 ~/ r 1 . 5 ~' ~ ~ 4.0 ;:

- ...................................................................... . ..
\~ 0~ f 1 ~ 5

5~: ~ ~ O
,, ' :
, .

0.7 , /~ O ,. ,.:

'.~
- Twenty 2nd instar nymphs were confined to 9 cm petri ~:
dishes containing the residue of the anti-juvenile hormone compound and all became precocious adults. Precocious :
adults were examined after 5 days for ovarian development and all were determined to be sterile. :~ ;
:

.. . - ,.
.. . . . .

Claims (11)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PRO-PERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A method of treating an insect to inhibit the juvenile hormone activity in said insect and thereby effect insect control which comprises contacting said insect with an effective amount sufficient to inhibit the effects of juvenile hormone with a compound having the following struc-ture:
wherein:
R and R1 are H or an alkyl, straight or branched chain, of 1 to 4 carbon atoms; R2 is hydrogen; R3 is hydrogen or alkoxy of 1 to 6 carbon atoms; R4 is alkoxy of 1 to 6 carbon atoms or R3 and R4 may be joined with a -OCH2O- group and R5 is hydrogen.

2. The method of claim 1 wherein the compound is 6, 7-dimethoxy-2, 2-dimethyl-3-chromene.

3. The method of claim 1 wherein the inhibition of juvenile hormone activity causes precocious maturation.

4. The method of claim 1 wherein the inhibition of juvenile hormone activity causes sterilization.

5. The method of claim 1 wherein the inhibition of juvenile hormone activity causes ovicidal activity.

6. The method of claim 1 wherein the inhibition of juvenile hormone activity causes induction of diapause.

7. A method for producing a chromene compound which comprises:
(a) reacting a compound of the formula wherein:
W is OH; and R2 and R5 are H, R3 alkoxy, of 1 to 6 carbon atoms, or H, R4 is alkoxy of 1 to 6 carbon atoms, or the structure wherein R3 and R4 are joined with a -OCH2O- group with a compound of the formulae wherein:
V is -COOH, -CH2OH, -CH2Br or -C?N
R and R1 are H lower alkyl, straight or branched chain, of 1 to 4 carbon atoms; in the presence of a Friedel-Crafts catalyst to produce a chromanone of the formula or a chromene of the formula:
wherein R and R1 through R5 are as stated previously:
(b) reacting the chromanone with a reducing agent to produce a chromanol; and (c) treating the chromanol with a dilute acid to produce a chromene or treating the chromane with a dehydro-genating agent to produce a chromene.

8. The method of claim 7 wherein, in step (a), 3, 4-dimethoxyphenol is reacted with 3, 3-dimethyl acrylic acid.

9. A compound having the following structure:
wherein:
R and R1 are H, or an alkyl, straight or branched chain, of 1 to 4 carbon atoms; R2 is hydrogen; R3 is hydrogen or alkoxy of 1 to 6 carbon atoms; R4 is alkoxy of 1 to 6 carbon atoms or R3 and R4 are joined with a -OCH2O- group and R5 is hydrogen with the proviso that R3 and R4 are not both methoxy when R and R1 are methyl.

10. A method which comprises contacting an insect with an anti-juvenile hormone selected from active compounds having the structure wherein R is methyl, R1 is methyl or ethyl, R3 is methoxy, ethoxy or H and R4 is an alkoxy containing 1 to 6 carbon atoms in an amount and concentration sufficient to alter the development of said insect.

11. The method of claim 10 wherein R4 is methoxy or ethoxy.