A compound of the formula ##STR1## wherein R is C.sub.3 -C.sub.10 normal- or branched- alkyl or cycloalkyl, C.sub.3 -C.sub.10 normal- or branched- alkyl or cycloalkyl having one or more halogen, cyano, C.sub.1 -C.sub.2 partially or completely halogenated alkyl, or C.sub.1 -C.sub.3 alkoxy or partially or completely halogenated alkoxy substituents, C.sub.3 -C.sub.10 cycloalkyl having C.sub.1 -C.sub.2 alkyl substituents, phenyl, or phenyl having one or more halogen, cyano, nitro, ethynl, C.sub.1 -C.sub.2 alkyl or partially or completely halogenated alkyl, or C.sub.1 -C.sub.3 alkoxy or partially or completely halogenated alkoxy substituents; wherein at least one of R.sub.2 -R.sub.6 is ethynyl; and wherein the remainder of R.sub.2 -R.sub.6 are independently either hydrogen, halogen, C.sub.1 -C.sub.2 alkyl, partially or completely halogenated C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.3 alkoxy, partially or completely halogenated C.sub.1 -C.sub.3 alkoxy, ethynyl, nitro, cyano, or azido. Such a compound is useful in killing pests, particularly insects.

TECHNICAL FIELD 
The present invention relates to pesticides which are 
1,4-bis-substituted-2,6,7-trioxabicyclo-[2.2.2]octanes wherein the 
1-position substituent is an ethynyl-substituted phenyl group. 
BACKGROUND OF THE INVENTION 
Pesticides are chemicals which combat the attacks of various pests on 
crops, livestock, man and their environment. They include insecticides, 
fungicides, herbicides (or weed killers), nematicides, molluscicides, 
acaricides and parasiticides. 
Many classes of compounds are known to exhibit pesticidal activity. 
Unfortunately, known pesticidal compositions may become less effective 
with time because of the development of resistance in the species against 
which they are used. Thus, there is a constant need for new types of 
pesticides. 
An ideal pesticide has high effectiveness in controlling pests, and is 
biodegradable. 
The present invention is concerned with providing pesticidal compositions 
having desirable properties such as those set forth above. 
DISCLOSURE OF THE INVENTION 
In accordance with an embodiment of the present invention, a compound is 
set forth having the formula 
##STR2## 
wherein R is C.sub.3 -C.sub.10 normal- or branched-alkyl or cycloalkyl, 
C.sub.3 -C.sub.10 normal- or branched-alkyl or cycloalkyl having one or 
more halogens, cyano, C.sub.1 -C.sub.2 partially or completely halogenated 
alkyl, or C.sub.1 -C.sub.3 alkoxy or partially or completely halogenated 
alkoxy substituents, C.sub.3 -C.sub.10 cycloalkyl having C.sub.1 -C.sub.2 
alkyl substituents, phenyl or phenyl having one or more halogen, cyano, 
nitro, ethynyl, C.sub.1 -C.sub.2 alkyl or partially or completely 
halogenated alkyl, or C.sub.1 -C.sub.3 alkoxy or partially or completely 
halogenated alkoxy substituent; wherein at least one of R.sub.2 -R.sub.6 
is ethynyl; and wherein the remainder of R.sub.2 -R.sub.6 are 
independently either hydrogen, halogen, C.sub.1 -C.sub.2 alkyl, partially 
or completely halogenated C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.3 alkoxy, 
partially or completely halogenated C.sub.1 -C.sub.3 alkoxy, ethynyl, 
nitro, azido or cyano. 
In accordance with another embodiment of the present invention a method of 
killing pests is set forth which comprises contacting the pests with an 
effective amount for killing the pests of a compound having the above 
formula. 
The preferred pesticidal compositions of the present invention have 
exceptionally high pesticidal activity, particularly when used with a 
synergist, and are biodegradable. In particular, they have been shown to 
exhibit significant pesticidal activity against the common housefly. 
BEST MODE FOR CARRYING OUT INVENTION 
In accordance with the present invention, a compound is provided having the 
formula (I) set forth above. It has been shown that this class of 
compounds includes a number of chemicals which exhibit very high 
pesticidal activity. 
Table 1, which follows, shows the effectiveness for control of houseflies 
of compounds which fall within the general formula (I), both alone and 
with the synergist piperonyl butoxide (PB). The abbreviations used in 
Table 1 are as follows: 
Pr--propyl, Bu--butyl, Hex--hexyl, Ph--phenyl, n--normal, t--tertiary, and 
c--cyclo. 
Other abbreviations which appear in later tables are as follows: 
Me--methyl, Et--ethyl, Pen--pentyl, Hept--heptyl, i--iso and s--secondary. 
TABLE 1 
______________________________________ 
Toxicity to Musca domestica both Alone and with the Synergist 
Piperonyl Butoxide of 1,4-Bis-Substituted-2,6,7-trioxabi- 
cyclo[2.2.2]octanes wherein the 1-Substituent is an 
Ethynyl-Substituted Phenyl Group 
LD.sub.50, .mu.g/g 
With 
Synergist 
4-Substituent 
1-Substituent (PB) Alone 
______________________________________ 
-n-Pr 4-ethynyl-Ph 0.043 0.75 
-c-Hex 4-ethynyl-Ph 0.030 0.53 
.sub.-t-Bu 
4-ethynyl-Ph 0.017 0.19 
______________________________________ 
Those pesticides of the formula (I) which have been tested have been found 
to exhibit a pesticidal activity, as LD.sub.50 in micrograms of the 
pesticide per gram of body weight of a selected pest, of no more than 
about 1. For example, such an activity has been shown as an insecticide 
against Musca domestica. The same pesticides, when used in combination 
with a synergist, e.g., PB, have been found to exhibit a pesticidal 
activity, as LD.sub.50 in micrograms of the pesticide per gram of body 
weight of a selected pest, of no more than about 0.1. Such an activity has 
also been shown as an insecticide against Musca domestica. Such high 
pesticidal activity against Musca domestica is not essential in as much as 
the compounds may show sufficient pesticidal activity against other pests 
as to make them useful against such other pests. 
The use of synergists with pesticides is well known and is discussed in 
detail in the publication "Mixed-Function Oxidase Involvement in the 
Biochemistry of Insecticide Synergists", J. E. Casida, J. Agric. Food 
Chem., 18, 753-772 (1970). The compounds of the present invention become 
even more effective with synergists which function to inhibit microsomal 
cytochrome P-450 oxidases that detoxify the pesticide thereby allowing a 
longer period for pesticidal action and consequently higher toxicity. Such 
synergists include those listed in the above publication plus other 
synergists which function in the manner stated. 
The compositions of the present invention may be used in combination with 
an inert carrier that serves as a diluent or vehicle for the active 
pesticides. For example, the toxicant may be dissolved in petroleum 
hydrocarbons, tetrahydrofuran, acetone, cellosolves or any other suitable 
inert carrier prior to use. Alternatively, the toxicant may be adsorbed on 
a solid inert carrier such as talc, clay, finely ground silica or the 
like. 
Contacting of pests with the pesticides of the present invention can be by 
any effective and convenient method, including any of the various methods 
of contacting well known in the art and used for delivering prior art 
pesticides to insects or other pests. For example, the pesticide may be 
utilized as a spray, an aerosol, dust or granules, or may be impregnated 
into or coated onto a structure with which the insect or other pests may 
come into contact, may be mixed with or impregnated into bait, may be 
incorporated with a substance or structure which slowly releases it in an 
area normally frequented by the pest or may be incorporated with and/or 
into other formulations which are directed into contact with the pest or 
placed where the pest will be likely to contact such formulations. The 
pesticides may be mixed with an inert carrier to facilitate delivery of 
the pesticides to the pests. 
The toxicity to houseflies is dependent on both the R substituent and the 
R.sub.2 -R.sub.6 substituents on the phenyl group (the subscripts 2, 3, 4, 
5 and 6 correspond to standard numbering of the aromatic ring positions). 
It has been previously demonstrated, as reported in applications Ser. Nos. 
692,818 and 575,843, that differing groups in the 1- and 4-position of the 
1,4-bis-substituted-2,6,7-trioxabicyclo[2.2.2]octanes (of the formula 
(II): R--C(CH.sub.2 O).sub.3 C--X) lead to different pesticidal 
activities. Tables 2-5, with the values in Tables 3-5 representing more 
refined evaluations than those in Table 2, illustrate the dependence of 
pesticidal activity on the 1- and 4-substituents of such 
1,4-bis-substituted compounds. 
TABLE 2 
______________________________________ 
Housefly Control by 1,4-bis-Substituted- 
2,6,7-trioxabicyclo[2.2.2]octanes Alone 
and With the Synergist Piperonyl Butoxide 
LD.sub.50, .mu.g/g 
R--C(CH.sub.2 O).sub.3 C--X 
Compound With 
R X number Synergist 
Alone 
______________________________________ 
.sub.-t-Bu 
4-BrPh 25 0.4 4 
-c-Hex 4-ClPh 8 0.4 37 
.sub.-t-Bu 
3,4-Cl.sub.2 Ph 
38 1 5 
-c-Hex -c-Hex 13 1 13 
.sub.-t-Bu 
4-ClPh 6 1 15 
-n-Pr 4-ClPh 2 2 10 
.sub.-t-Bu 
-c-Hex 60 2 40 
-c-Hex 4-FPh 24 2 &gt;500 
.sub.-t-Bu 
4-FPh 23 3 &gt;500 
.sub.-t-Bu 
3-ClPh 21 4 125 
-n-Bu 4-ClPh 4 4 23 
Ph - c-Hex 14 5 225 
-c-Hex Ph 18 5 &gt;500 
Ph 4-ClPh 9 7 400* 
.sub.-i-Pr 
-c-Hex 59 8 &gt;500 
.sub.-i-Pr 
4-ClPh 3 12 100 
.sub.-t-Bu 
Ph 17 23 &gt;500 
.sub.-t-Bu 
2-FPh 19 25 &gt;500 
.sub.-t-Bu 
-n-Bu 51 50 450 
-n-Pr Ph 15 60 &gt;500 
-n-Pr -n-Bu 69 100 &gt;500 
.sub.-t-Bu 
Ethynyl 65 125 150 
.sub.-t-Bu 
Benzyl 68 125 &gt;500 
.sub.-i-Pr 
Ethynyl 64 125 &gt;500 
Et c-Hex 12 225 &gt;500 
Ph 4-FPh 45 225 &gt;500 
Ph Ph 44 250 &gt;500 
.sub.-t-Bu 
-n-Pr 49 375 &gt;500 
4-MePh 4-ClPh 10 &gt;150 &gt;150 
.sub.-t-Bu 
H 46 &gt;500 &gt;500 
.sub. -t-Bu 
Me 47 &gt;500 &gt;500 
.sub.-t-Bu 
Et 48 &gt;500 &gt;500 
.sub.-t-Bu 
.sub.-i-Pr 
50 &gt;500 &gt;500 
.sub.-t-Bu 
4- .sub.-t-BuPh 
37 &gt;500 &gt;500 
.sub.-i-Pr 
Vinyl 63 &gt;500 &gt;500 
.sub.-i-Pr 
3-PhOPh 22 &gt;500 &gt;500 
.sub.-i-Pr 
1-BrEt 66 &gt;500 &gt;500 
.sub.-i-Pr 
1,2-Br.sub.2 Et 
67 &gt;500 &gt;500 
NO.sub.2 
4-ClPh 11 &gt;500 &gt;500 
______________________________________ 
*Value based on suspension in acetone with only partial solution. 
TABLE 3 
______________________________________ 
Effect of R-Substituent on the Topical 
Toxicity to Houseflies of 1-(4-Chlorophenyl)-2,6,7- 
trioxabicyclo[2.2.2]octanes and Three 1-Cyclohexyl Analogs 
compound LD.sub.50, .mu.g/g, with 
R-substituent 
number PB (and alone) 
______________________________________ 
Et.sup.a 1 105 (&gt;500) 
-n-Pr 2 2.5 (23) 
.sub.-i-Pr 
3 8.3 (140) 
-n-Bu 4 3.5 (17) 
.sub.-s-Bu 
5 2.7 (58) 
.sub.-t-Bu 
6 1.5 (10) 
-c-Pen 7 2.0 (21) 
-c-Hex.sup.a 
8 0.53 (10) 
Ph.sup.a 9 2.5 (41) 
4-MePh 10 &gt;500 (&gt;500) 
NO.sub.2 11 &gt;500 (&gt;500) 
______________________________________ 
.sup.a Compound numbers and LD.sub.50 values [.mu.g/g with PB (and alone) 
in the 1-cHex series are: (12) 4Et 350 (&gt;500); (13) 4-cHex 0.63 (8.5); 
(14) 4Ph 7.0 (375). 
TABLE 4 
__________________________________________________________________________ 
Effect of Substitution on 1-Phenyl Group (X) on the Topical Toxicity to 
Houseflies of 
4-Alkyl-2,6,7-trioxabicyclo[2.2.2]octanes and Two 4-Phenyl Analogs 
substituent 
on 1-phenyl 
compound number LD.sub.50, .mu.g/g, with PB (and alone) 
group (X) 
4- -n-Pr 
4- .sub.-i-Pr 
4- .sub.-t-Bu 
4- -c-Hex 
4- -n-Pr 
4- .sub.-i-Pr 
4- .sub.-t-Bu 
4- -c-Hex 
__________________________________________________________________________ 
H.sup.a 
15 16 17 18 90 (&gt;500) 
90 (&gt;500) 
23 (&gt;500) 
13 (&gt;500) 
2-F 19 30 (&gt;500) 
2-Cl 20 105 (&gt;500) 
3-Cl 21 6.3 (375) 
3-PhO 22 &gt;500 
(&gt;500) 
4-F.sup.a 23 24 5.5 (&gt;500) 
1.9 
(&gt;500) 
4-Cl 2 3 6 8 2.5 (23) 
8.3 (140) 
1.5 (10) 
0.53 
(10) 
4-Br 25 26 0.83 
(3.5) 
0.25 
(6.5) 
4-CF.sub.3 27 53 (&gt;500) 
4-NO.sub.2 
28 29 11 (&gt;500) 
5.0 (&gt;500) 
4-CN 30 31 0.23 
(4.8) 
0.65 
(115) 
4-N.sub.3 32 13 (160) 
4-MeSO.sub.2 
33 &gt;500 
(&gt;500) 
4-MeS 34 &gt;500 
(&gt;500) 
4-MeO 35 265 (&gt;500) 
4-Me 36 250 (&gt;500) 
4- .sub.-t-Bu 37 &gt;500 
(&gt;500) 
3,4-Cl.sub.2 38 39 0.88 
(4.3) 
2.5 
(30) 
3-NO.sub.2,4-Cl 
40 &gt;500 
(&gt;500) 
3,4-OCH.sub.2 O 
41 &gt;500 
(&gt;500) 
2,3,4,5,6-F.sub.5 
42 43 135 (&gt;500) 
18 (240) 
__________________________________________________________________________ 
.sup.a Compound numbers and LD.sub.50 values [.mu.g/g, with PB (and 
alone)] in the 4Ph series are (44) H 325 (&gt;500) and (45) 4F 250 (&gt;500). 
TABLE 5 
______________________________________ 
Effect of 1-Substituent (X) on the Topical Toxicity to House- 
flies of 4-Isopropyl- and 4- .sub.-t-Butyl-2,6,7-trioxabicyclo[2.2.2]- 
octanes and Five 4- -n-Propyl and two 4-Cyclohexyl Analogs 
1-substit- 
compound no. LD.sub.50, .mu.g/g, with PB (and alone) 
uent (X) 
4- .sub.-i-Pr 
4- .sub.-t-Bu 
4- .sub.-i-Pr 
4- .sub.-t-Bu 
______________________________________ 
H 46 &gt;500 (&gt;500) 
Me 47 &gt;500 (&gt;500) 
Et 48 &gt;500 (&gt;500) 
-n-Pr 49 425 (&gt;500) 
.sub.-i-Pr 50 &gt;500 (&gt;500) 
-n-Bu.sup.a 51 55 (450) 
.sub.-s-Bu 
52 &gt;500 (&gt;500) 
-n-Pen 53 33 (365) 
--neo-Pen 
54 &gt;500 (&gt;500) 
-n-Hex 
55 160 (&gt;500) 
-c-Pr 56 &gt;500 (&gt;500) 
-c-Bu 57 &gt;500 (&gt;500) 
-c-Pen 
58 500 (&gt;500) 
-c-Hex.sup.a 
59 60 14 (&gt;500) 
3.5 (165) 
-c-Hept.sup.a 
61 62 8.5 (300) 2.0 (44) 
Vinyl 63 &gt;500 (&gt;500) 
Ethynyl 
64 65 325 (&gt;500) 
90 (175) 
1-BrEt 66 &gt;500 (&gt;500) 
1,2-Br.sub.2 Et 
67 &gt;500 (&gt;500) 
Benzyl 68 210 (&gt;500) 
______________________________________ 
.sup.a Compound numbers and LD.sub.50 values [.mu.g/g with PB (and alone) 
are: in the 4-nPr series (69) 1-nBu 155 (&gt;500), (70) 
1(1-bicyclo[2.2.1]heptyl) 125 (&gt;500), (71) 1(2-bicyclo[2.2.1] heptyl) 10 
(160), (72) 1(cyclohex-3-enyl) 19 (110) and (73) 1(5-bromo-2-furyl) 68 
(500): in the 4-cHex series (13) 1-cHex 0.63 (8.5) and (74) 1-cHept 2.0 
(13). 
The effect of the R-substituent on the effectiveness of the toxicants both 
alone and along with PB on houseflies is presented in Table 3. 
The effect of substitution on the 1-phenyl group on the topical toxicity to 
houseflies of 4-alkyl-2,6,7-trioxabicyclo[2.2.2]octanes and of two 
4-phenyl analogs was tested. Table 4 presents the results of the testing. 
The effect of the 1-substituent on the topical toxicity to houseflies of 
4-isopropyl- and of 4-t-butyl-2,6,7-trioxabicyclo[2.2.2]octanes and of 
five 4-n-propyl and two 4-cyclohexyl analogs was also tested. Table 5 
presents the results of the testing. 
Tables 2-5 illustrate the fact that the effectiveness of compounds of the 
general formula (II) R--C(CH.sub.2 O).sub.3 C--X, wherein R and X 
represent organic substituents, is dependent on the nature of both the R 
and the X component. Table 6, which follows, shows the toxicity to 
American cockroaches of various topically-applied 
1,4-bis-substituted-2,6,7-trioxabicyclo[2.2.2]octanes. 
TABLE 6 
______________________________________ 
Toxicity to American Cockroaches of Topically-Applied 
1,4-bis-Substituted-2,6,7-trioxabicyclo[2.2.2]octanes 
R--C(CH.sub.2 O).sub.3 C--X 
compound 
R X number LD.sub.50 .mu.g/g, with PB 
______________________________________ 
-n-Pr 4-ClPh 2 2 
-n-Bu 4-ClPh 4 3 
.sub.-t-Bu 
4-ClPh 6 .sup. 1.sup.a 
-c-Pen 4-ClPh 7 2 
-c-Hex 4-ClPh 8 .sup. 1.sup.a 
Ph 4-ClPh 9 7 
-c-Hex -c-Hex 13 &gt;8 
.sub.-t-Bu 
4-BrPh 25 .sup. 1.sup.a 
-c-Hex 4-BrPh 26 1 
.sub.-t-Bu 
3,4-Cl.sub.2 Ph 
38 &gt;10 
.sub.-t-Bu 
-c-Hex 60 .sup. 2.sup.a 
______________________________________ 
.sup.a At least 20fold synergism by PB. 
The data in Tables 2-5 indicate that compounds of the formula R--C(CH.sub.2 
O).sub.3 C--X are often effective pesticides. R or X may be alkyl, 
alkenyl, alkynyl, cycloalkyl or cycloalkenyl, each of which may be normal, 
branched or substituted, or may be aryl or substituted aryl or 
heterocycle. When R is a normal or branched alkyl, or cycloalkyl or aryl, 
useful compounds result. Preferably, the number of carbon atoms in R is 
three to ten. More preferably R is n-propyl, t-butyl, cyclohexyl, 
cyclopentyl, i-propyl, n-butyl, s-butyl or phenyl. X is preferably 
cycloalkyl or substituted cycloalkyl or cycloalkenyl having six to ten 
carbon atoms, normal alkyl, alkynyl, substituted alkyl or substituted 
alkynyl, or substituted phenyl. Effective pesticides result with 
cyclohexyl and cycloheptyl substituents. Other useful substituents include 
n-pentyl, cyclohex-3-enyl and 2-bicyclo[2.2.1]heptyl. The substituents on 
the phenyl group, when the phenyl group is the group X, are preferably 
halogens, cyano, nitro or azido groups. 
The data in Table 1 illustrate the very high pesticidal effectiveness of 
compounds of formula (I) in accordance with the present invention. It is 
apparent from the data in Tables 1-6 that R (in formula (I)) may be alkyl, 
alkenyl, alkynyl, cycloalkyl or cycloalkenyl, each of which may be normal, 
branched or substituted, or may be aryl or substituted aryl or 
heterocycle. When R is a normal or branched alkyl, or cycloalkyl or aryl, 
particularly useful compounds result. Preferably, the number of carbon 
atoms in R, when R is normal- or branched-alkyl or cycloalkyl, is 3 to 10. 
The C.sub.3 -C.sub.10 normal- or branched-alkyl or cycloalkyl groups may 
have one or more halogens, cyano, C.sub.1 -C.sub.2 partially or completely 
halogenated alkyl or C.sub.1 -C.sub.3 alkoxy or partially or completely 
halogenated alkoxy substituents. The C.sub.3 -C.sub.10 cycloalkyl may have 
C.sub.1 -C.sub.2 alkyl substituents. When R is aryl, it may be phenyl or 
phenyl having one or more halogen, cyano, ethynyl, nitro, azido, C.sub.1 
-C.sub.2 alkyl or partially or completely halogenated alkyl, or C.sub.1 
-C.sub.3 alkoxy or partially or completely halogenated alkoxy 
substituents. 
It is essential to the practice of the present invention that at least one 
of R.sub.2 -R.sub.6 be ethynyl. The remainder of R.sub.2 -R.sub.6 are 
independently either hydrogen, halogen, C.sub.1 -C.sub.2 alkyl, partially 
or completely halogenated C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.3 alkoxy, 
partially or completely halogenated C.sub.1 -C.sub.3 alkoxy, ethynyl, 
nitro, azido or cyano. Preferably, at least one of R.sub.3, R.sub.4 and 
R.sub.5 is ethynyl and the remainder of R.sub.2 -R.sub.6 are hydrogen, 
fluorine, chlorine, bromine, cyano, CF.sub.3, ethynyl, methyl, ethyl, 
methoxy, ethoxy, nitro or azido. Pesticidal activity has been demonstrated 
when one of R.sub.3, R.sub.4 and R.sub.5 is hydrogen. Such activity has 
also been shown when at least two of R.sub.3, R.sub.4 and R.sub.5 are 
hydrogen. Particularly effective compounds have been formulated wherein 
R.sub.3 and R.sub.5 are hydrogen and R.sub.4 is ethynyl. 
In accordance with an embodiment of the present invention pests may be 
killed by a method comprising contacting the pests, with an effective 
amount for killing them, of a compound with formula (I) wherein R and 
R.sub.2 -R.sub.6 are as set forth above for formula (I). Pesticidal 
activity is enhanced through use of a synergist. 
Procedures of Synthesis 
Methods for making compounds of the formula R--C(CH.sub.2 O).sub.3 C--X 
(II) can be found in the following publications. "Structure-Toxicity 
Relationships of 1-Substituted-4-alkyl-2,6,7-trioxabicyclo[2.2.2]octanes," 
D. S. Milbrath, J. L. Engel, J. G. Verkade and J. E. Casida, Toxicology 
and Applied Pharmacology, 47, 287-293 (1979); "Structure-Toxicity 
Relationships of 2,6,7-Trioxabicyclo[2.2.2]octanes and Related Compounds," 
J. E. Casida, M. Eto, A. D. Moscioni, J. L. Engel, D. S. Milbrath and J. 
G. Verkade, "Toxicology and Applied Pharmacology, 36, 261-279 (1976); 
"Nuclear Magnetic Resonance in Polycyclic Compounds. II. Long-Range 
H.sup.1 -H.sup.1 and H.sup.1 -P.sup.31 Coupling in Some Adamantane and 
Bicyclo[2.2.2]octane Derivatives," E. J. Boros, K. J. Coskran, R. W. King 
and J. G. Verkade, JACS, 88, 1140-1143 (1966); "Unusual Behavior of 
Hexafluorobenzene and Benzene in the Aromatic Nuclear Magnetic Resonance 
Shift Effect," R. D. Bertrand, R. D. Compton and J. G. Verkade, JACS, 92, 
2702-2709 (1970 ); "A New General Synthetic Route to Bridged Carboxylic 
Ortho Esters," E. J. Corey and N. Raju, Tetrahedron Letters, 24, 5571-5574 
(1983); and "Bicyclo Ortho Esters by Direct Esterification," R. A. Barnes, 
G. Doyle, and J. A. Hoffman, J. Org. Chem., 27, 90-93 (1962). 
Intermediates for these reactions are described by "Ketene Acetals. XXXIV. 
Tetra- and Pentamethylene Ketene Acetals," S. M. McElvain and R. E. Starn, 
Jr., JACS, 77, 4571-4577 (1955); "Preparation of Trimethylolisobutane by 
Condensation of Isovaleraldehyde with Formaldehyde," M. M. Ketslakh, D. M. 
Rudkovskii, and F. A. Eppel, Oksosintez, Poluchenie Metodom Oksosinteza 
Al'degidov, Spritov i Vtorichnykh Produktov na ikh Osnove, Vses. 
Nauchn.-Issled., Inst. Neftekhim Protsessov (1963), 156-163; "Extensions 
of Tollens Condensation," O. C. Dermer and P. W. Solomon, JACS, 76, 
1697-1699 (1954); and "Cyclic Ethers Made by Pyrolysis of Carbonate 
Esters", D. B. Pattison, JACS, 79, 3455-3456 (1957). 
Three specific methods (A-C) have been used to prepare 
trioxabicyclooctanes. Each procedure started from a triol synthesized from 
the corresponding substituted-acetaldehyde by hydroxymethylation and 
subsequent crossed-Cannizzaro reaction (Dermer and Solomon, 1954; Ketslakh 
et al., 1963). The reaction scheme was: 
##STR3## 
Each trioxabicyclooctane gave appropriate proton nuclear magnetic 
resonance and mass spectrometry (MS) characteristics. 
Procedure A 
Acid-catalyzed Condensation of a Triol with an Orthocarboxylate (Boros et 
al., 1966; Bertrand et al., 1970). The equation for the reaction being: 
##STR4## 
where R' may be alkyl or aryl, preferably methyl or ethyl. For example, a 
mixture of 2-t-butyl-2-hydroxymethyl-1,3-propanediol (R=t--Bu) (0.4 g, 2.5 
mmol), trimethyl orthocyclohexanecarboxylate (X=c--Hex; R'=CH.sub.3), (0.5 
g, 2.5 mmol) and 4-toluenesulphonic acid (10 mg) was heated to 160.degree. 
C. until methanol distilled over. The residue was vacuum dried (at 1 mm 
Hg) and then passed down a short basic alumina column to give 
trioxabicyclooctane 60 (X=c--Hex; R=t--Bu) (0.6 g, 95%). Directly 
analogous procedures were used to prepare compounds 1-19, 21-27, 37-39, 
44-51, 59 and 63-69. 
Intermediate trimethyl orthocarboxylates were commercially available or 
were synthesized by either of two procedures illustrated with the methyl 
esters. In the first procedure, the appropriate benzotrichloride or 
benzotribromide (from bromination of the corresponding toluene with 
N-bromosuccinimide (NBS)) was subjected to halide displacement with 
methoxide (McElvain and Venerable, 1950). These methods were as follows: 
##STR5## 
wherein Y represents hydrogen or one or more other groups such as halo or 
trifluoromethyl. 
In the second procedure, the appropriate nitrile was treated with methanol 
and hydrochloric acid to obtain the imino ester hydrochloride and 
ultimately the trimethyl orthocarboxylate (McElvain and Starn, 1955). This 
procedure was as follows: 
##STR6## 
Procedure B 
Rearrangement of an Acylated Hydroxymethyloxetane (Corey and Raju, 1983). 
Acylation of 3-substituted-3-hydroxymethyloxetanes (prepared from the 
appropriate triol via pyrolysis of the carbonate ester) (Pattison, 1957) 
gives the corresponding oxetane esters which can be rearranged in the 
presence of boron trifluoride etherate to form trioxabicyclooctanes. The 
equation for the reaction being: 
##STR7## 
For example, 4-nitrobenzoyl chloride (2.28 g, 12.3 mmol) in dry 
dichloromethane (4 ml) was added to 3-isopropyl-3-hydroxymethyloxetane 
(1.6 g, 12.3 mmol) in dry dichloromethane (15 ml) and dry pyridine (2 ml) 
at 0.degree. C. under a nitrogen atmosphere. The solution was stirred 
overnight, then extracted with water, dried (sodium sulfate), filtered and 
evaporated to leave the 4-nitrobenzoyl ester (3.4 g, 99%) as a residue 
which was not purified further. .sup.1 H NMR (CDCl.sub.3), .delta. 1.0 
[6H, d, (CH.sub.3).sub.2 C], 2.3 [1H, m, C-CH], 4.55 [2H, s, CH.sub.2 
OCO], 4.6 [4H, d of d, CH.sub.2 OCH.sub.2 ], 8.3 [4H, q, aromatic]. This 
residue was dissolved in dry dichloromethane (15 ml) under a nitrogen 
atmosphere, cooled to -55.degree. C. and boron trifluoride etherate (2 ml) 
was added. The mixture was allowed to warm to room temperature and was 
then quenched with triethylamine, evaporated to dryness and partitioned 
between dichloromethane and water. The organic layer was separated, dried 
(potassium carbonate) and evaporated. The residue was purified by passage 
through a short basic alumina column to afford trioxabicyclooctane 28 
(X=4--NO.sub.2 Ph; R=i--Pr) (1.7 g, 50%). Directly analogous procedures 
were used to prepare compounds 16, 20, 29-36, 40-43, 53-58, 61, 62 and 
70-74. 
Procedure C 
Acid-catalyzed Condensation of a Triol Directly with a Carboxylic Acid, 
Acid Chloride, or the like (Barnes et al., 1962). The equation for the 
reaction being: 
##STR8## 
wherein Z represents hydroxyl, halo, acyl, cyano, or other group which it 
is suitable and customary to use in condensation reactions. Thus, a 
solution of 2-isopropyl-2-hydroxymethyl-1,3-propanediol (3 g, 20 mmol), 
2-methylbutyric acid (2 g, 20 mmol) and 4-toluenesulphonic acid (20 mg) in 
benzene (100 ml) was heated to reflux for 12 hours and the water formed 
was separated off. The solution was evaporated down to low volume and then 
distilled under reduced pressure to give trioxabicyclooctane 52 (X=s--Bu; 
R=i--Pr) (2.55 g, 62%). 
The 4-substituted-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octanes of 
formula (I) were prepared via Procedure B above. Acylation of 
3-substituted-3-hydroxymethyloxetanes with 4-(1,2-dibromoethyl)benzoyl 
chloride gave the corresponding oxetane esters which were rearranged in 
the presence of boron trifluoride etherate to form the 
4-substituted-1-(4-[1,2-bromoethyl]phenyl)-2,6,7-trioxabicyclo[2.2.2]octan 
es. These in turn were dehydrobrominated using sodamide in liquid ammonia 
to give the 
4-substituted-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octanes. 
Equations for the reactions are:

The synthesis procedure for compounds in accordance with the present 
invention will be better understood by reference to the following 
illustrative procedures. 
Procedure 1 
Preparation of 4-(1,2-dibromoethyl)benzoyl chloride 
To a solution of p-vinylbenzoic acid (5 g, 34 mmol) in chloroform (50 ml) 
at 0.degree. C. was added Br.sub.2 (35 mmol) in chloroform with stirring. 
The mixture was allowed to stand overnight and then was evaporated to 
dryness, leaving crude 4-(1,2-dibromoethyl)benzoic acid, 10.4 g (99%). 
This was suspended in dry benzene (100 ml), thionyl chloride (8.3 g) was 
added and the mixture was heated sufficiently to cause it to reflux for 3 
hours. The solution was evaporated to dryness to give the acid chloride as 
a solid. 
Procedure 2 
Preparation of 
4-t-butyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octane 
To a stirred solution of 3-t-butyl-3-hydroxymethyloxetane (2.16 g, 15 mmol) 
in dry dichloromethane (30 ml) containing pyridine (1.5 ml) at 0.degree. 
C. under a nitrogen atmosphere was added a solution of 
4-(1,2-dibromoethyl)benzoyl chloride (5 g, 16 mmol) which was produced in 
accordance with Procedure 1. The mixture was allowed to warm to room 
temperature and was stirred overnight. The resulting solution was washed 
with water, dried over sodium sulfate and evaporated to leave the oxetane 
ester, 6.5 g. The product was characterized by NMR (300 MHz, CDCl.sub.3) 
.delta. 1.05 (9H, s, (CH.sub.3).sub.3 C), 3.95-4.1 (2H, m, CH.sub.2 Br), 
4.45 (2H, s, CH.sub.2 --O), 4.6 (4H, d of d, CH.sub.2 --O--CH.sub.2), 5.15 
(1H, d of d, Ar--CHBr), 7.5 (2H, d, aromatic), 8.1 (2H, d, aromatic). 
To a stirred solution of the oxetane ester (6.5 g, 15 mmol) in dry 
dichloromethane (35 ml) under a nitrogen atmosphere at -70.degree. C. was 
added boron trifluoride etherate (1 ml). The solution was allowed to warm 
to room temperature and was stirred overnight. The reaction mixture was 
quenched with dry triethylamine and evaporated to dryness. The residue was 
partitioned between water and dichloromethane and the organic layer was 
separated, dried over K.sub.2 CO.sub.3 and evaporated to leave crude 
4-t-butyl-1-(4-(1,2-dibromoethyl)phenyl)-2,6,7-trioxabicyclo[2.2.2]octane. 
This compound was characterized by NMR (300 MHz, CDCl.sub.3), .delta. 0.9 
(9H, s, (CH.sub.3).sub.3 C), 3.9-4.05 (2H, m, CH.sub.2 Br), 4.15 (6H, s, 
(CH.sub.2 O).sub.3), 5.1 (1H, d of d, ArCHBr), 7.35 (2H, d, aromatic), 7.6 
(2H, d, aromatic). 
Small pieces of sodium were added to liquid ammonia until a blue color 
persisted. Ferric nitrate (100 mg) was added and the solution was stirred. 
When the solution turned colorless, sodium (6 g) was added in small 
pieces. After about 30 to 35 minutes following the addition the blue color 
disappeared and a solution of the above dibromoethylphenyl bicyclooctane 
in tetrahydrofuran was added to the solution. The ammonia was allowed to 
evaporate overnight and the residue was partitioned between ether and 
ice/water. The organic layer was separated, dried over K.sub.2 CO.sub.3 
and evaporated to leave crude 1-(4-ethynylphenyl)bicyclooctane. This was 
purified by chromatography on alumina (made basic with NH.sub.3) and 
elution with dichloromethanehexane (1:4) and recrystallization from 
hexanedichloromethane. The compound was characterized by NMR (300 MHz, 
CDCl.sub.3): .delta. 0.9 (9H, s, (CH.sub.3).sub.3 C), 3.05 (1H, s, 
C.tbd.CH), 4.15 (6H, s, (CH.sub.2 O).sub.3), 7.45 (2H, d, aromatic), 7.55 
(2H, d, aromatic). The compound was also characterized by mass 
spectrometry (M.sup.+ 272) and was found to have a melting point of 
167.degree.-168 C. 
Procedure 3 
Preparation of 
4-cyclohexyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octane 
Utilizing Procedure 2, 
4-cyclohexyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octane was 
prepared from its respective oxetane. The 
3-cyclohexyl-3-hydroxymethyloxetane was reacted with 
4-(1,2-dibromoethyl)benzoyl chloride by the method of Procedure 2. The 
resulting product was characterized by NMR (300 MHz, CDCl.sub.3): .delta. 
1.0-1.4 and 1.6-2.0 (11H, m, cyclohexyl CH.sub.2), 3.9-4.1 (2H, m, 
CH.sub.2 Br), 4.4 (2H, s, CH.sub.2 O), 4.55 (4H, d of d, CH.sub.2 
OCH.sub.2), 5.1 (1H, d of d, ArCHBr), 7.45 (2H, d, aromatic), 8.1 (2H, d, 
aromatic). 
The oxetane ester produced by the above reaction was reacted with boron 
trifluoride etherate as described in Procedure 2 to yield 
4-cyclohexyl-1-(4-(1,2-dibromoethyl)phenyl)-2,6,7-trioxabicyclo[2.2.2]octa 
ne. The product was characterized by NMR (300 MHz, CDCl.sub.3): .delta. 
0.9-1.3 and 1.5-1.9 (11H, m, cyclohexyl CH.sub.2), 3.9-4.1 (2H, m, 
CH.sub.2 Br), 4.1 (6H, s, (CH.sub.2 O).sub.3), 5.1 (1H, d of d, ArCHBr), 
7.35 (2H, d, aromatic), 7.6 (2H, d, aromatic). 
The dibromoethylphenyl bicyclic was dehydrobrominated in accordance with 
the Procedure 2 to yield the desired 
4-cyclohexyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octane. The 
product was characterized by NMR (300 MHz, CDCl.sub.3): .delta. 0.9-1.3 
and 1.6-1.9 (11H, m, cyclohexyl CH.sub.2), 3.05 (1H, s, C.tbd.CH), 4.1 
(6H, s, (CH.sub.2 O).sub.3), 7.45 (2H, d, aromatic), 7.55 (2H, d, 
aromatic). It was also characterized by mass spectometry ([M+1].sup.+ 
=299) and was found to have a melting point of 190.degree.-192.degree. C. 
Procedure 4 
Preparation of 
4-n-propyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2.]octane 
The compound 
4-n-propyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octane was 
synthesized utilizing the method set forth in Procedure 2. Reaction of the 
3-n-propyl-3-hydroxymethyloxetane with 4-(1,2-dibromoethyl)benzoyl 
chloride led to the production of the corresponding oxetane ester which 
was characterized by NMR (300 MHz, CDCl.sub.3): .delta. 0.95 (3H, t, 
CH.sub.3), 1.35 (2H, m, CH.sub.3 CH.sub.2), 1.75 (2H, m, CH.sub.3 CH.sub.2 
CH.sub.2), 3.95-4.1 (2H, m, CH.sub.2 Br), 4.45 (2H, s, CH.sub.2 O), 
4.5-4.6 (4H, d of d, CH.sub.2 OCH.sub.2), 5.1 (1H, d of d, ArCHBr), 7.5 
(2H, d, aromatic), 8.05 (2H, d, aromatic). The oxetane ester was reacted 
with boron trifluoride etherate as described in Procedure 2 to provide 
4-n-propyl-1-(4-(1,2-dibromoethyl)phenyl)-2,6,7-trioxabicyclo[2.2.2]octane 
. This compound was characterized by NMR (300 MHz, CDCl.sub.3): .delta. 0.9 
(3H, t, CH.sub.3), 1.15-1.35 (4H, m, CH.sub.2 CH.sub.2), 3.9-4.1 (2H, m, 
CH.sub.2 Br), 4.1 (6H, s, (CH.sub.2 O).sub.3), 5.1 (1H, d of d, ArCHBr), 
7.35 (2H, d, aromatic), 7.6 (2H, d, aromatic). 
The dibromo compound was dehydrobrominated to form the corresponding 
ethynyl compound, 
4-n-propyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octane by the 
method set forth in Procedure 2. The resulting product was characterized 
by NMR (300 MHz, CDCl.sub.3): .delta. 0.9 (3H, t, CH.sub.3), 1.15-1.35 
(4H, m, CH.sub.2 CH.sub.2), 3.05 (1H, s, C.tbd.CH), 4.1 (6H, s, (CH.sub.2 
O).sub.3), 7.45 (2H, d, aromatic), 7.55 (2H, d, aromatic). The compound 
was further characterized by mass spectometry ([M+1].sup.+ =259) and was 
found to have a melting point of 127.degree.-129.degree. C. 
Procedure 5 
Biological Activity Determination LD.sub.50 for Musca domestica 
The compounds listed in Tables 1-5 were tested for insecticidal activity by 
dissolving them in acetone or in tetrahydrofuran if they were insoluble in 
acetone. Subsequent dilutions were prepared using the same solvent. The 
compound solutions (0.5 microliter) were applied topically to the ventrum 
of the abdomen of anesthetized adult female houseflies (Musca domestica 
L., SCR strain, 3-5 days after emergence, 20 mg each). The toxicity 
studies were varied by treating the houseflies topically with PB at 250 
micrograms per gram, two to three hours prior to administering the 
toxicant. The treated houseflies were provided sugar and water, and 
mortality was determined after 24 hours at 25.degree. C. The data in 
Tables 1-5 are reported at the lethal dose, in micrograms of toxicant per 
gram of insect weight required to kill 50% of the fly population and are 
referred to as the LD.sub.50 values. 
LD.sub.50 for Periplaneta americana 
The compounds listed in Table 6 were tested for toxicity to adult male 
American cockroaches (Periplaneta americana) by applying test solutions, 
as with Musca domestica, to the thorax using 1.0 microliter carrier 
solvent per insect. In each case the cockroaches were also tested after 
topical pretreatment with PB at 250 microgram/gram 2 hours before 
administering the trioxabicyclooctane. LD.sub.50 values were established 
after 24 hours at 25.degree. C. The compounds tested are strongly 
synergized by PB to achieve a potency similar to that with PB-treated 
houseflies except for two compounds (13 and 38) which are more than 
tenfold more toxic to houseflies than to cockroaches. 
Other similar toxicity tests showed that compound 6 is also toxic to the 
mosquito larva, black bean aphid, German cockroach and milkweed bug. Thus, 
the wide range of usefulness of the new class of pesticides set forth 
herein has been established. 
Industrial Applicability 
The compounds of the present invention which have been synthesized have 
been found to have significant activity as pesticides. Furthermore, they 
are readily biodegradable.