Note: Descriptions are shown in the official language in which they were submitted.
PR-5285C
INSECT REPELLENT COMPOUNDS
Back~round of the Invention
This invention relates to novel compounds having
the formula ~ (CH2)n - ~ -R
in which R is C3-C5 alkyl or C3-C5 alkenyl and n is an
integer from 1 to 3. The terms "alkyl" and "alkenyl" in-
clude both straight and branched chain groups. In a pre-
ferred embodiment, n is 3 and R is 2-methyl-l-propenyl,
-CH=C(CH3)2o A preferred compound of this type is gamma-
(3-p~ridyl)--propyl-3-methyl-2-butenoate (nG3, R=2-methyl-1-
propenyl, and the ester moiety is substituted at the 3-
position on the pyridyl ring). Other compounds include
the 2-pyridyl and 4-pyridyl isomers o~ this preferred com-
pound, the methyl analog (n=l, R=2-methyl-l-propenyl,
sub~titution at the 3-position on the ring) and ga~ma-(3-
pyridyl)-propyl isovaLerate (n~3, R=isobutyl, ~ubstitu~ion
at the 3-pvsition on the ring).
The compounds of this type can be prepared by
reaction o~ an appropriate pyridyl alkanol with an acyl
chloride:
(~H2)nOH + R~Cl >
(CH2)nO - ~ -R + HCl
'S7~'~
--2--
The reaction is generally conducted at tempera-
tures of about 5-15C., in the presence of a solvent such
as methylene chloride, chloroform, other chloro-carbon
solvents or ethers, and a hydrogen chloride acceptor,
For preparation of compounds in which R is alkyl, suitable
hydrogen chloride acceptors include pyridine, triethylamine
and sodium hydroxide. For compounds in which R is alkenyl,
pyridine is used. The product is recovered by conventional
extraction, washing and filtration steps.
Preparation of such compounds is illustrated by
the following example.
Example 1
Preparation of Gamma-(3-PyridYl)-Propyl-3-Methyl-2-Butenoate
Into a flask was introduced a solution of 5.00
grams (0.036 mole) of 3-(3-pyridyl)-1-propanol and 3.16
grams (0.040 mole) pyridine ~reagent grade) in 50 milli-
liters of methylene chloride (reagent grade). A clear
brown solution was formed which was then cooled to 0C.
with an ice-water bath. There was then added 4.74 grams
(0.040 mole) of 3,3-dimethylacryloyl chlorid~ (97% pure),
dropwise, over a period of 10 minutes~ the temperature
being maintained between 5 and 15C. The solution be-
came deep red. Following the addition, the solution was
stirred at 0C. for one hour; the cooling bath was
removed and the solut~on stirred at room temperature
for three additional hours.
The solution was then diluted with 50 milli-
liters of methylene chloride and poured into 50 milli-
liters of water; the organic layer was separated and
washed with 10 milliliters of a saturated sodium bi-
carbonate solution and three portions each of 10
milliliters of wa~er until the pH of the solution was
measured at 7, followed by washing with 10 milliliters
of sodium chloride and drying ~ver sodium sulfate. The
--3--
dried organic solution was filtered through sodium sulfate
and the solvent was removed under vacuum to yield 8.08 grams
(101.3% o~ theoretical) of the desired compound, a crude
clear orange oil, n30 1.5153. The structure of the
compound was confirmed by Infrared and nuclear magnetic
resonance spectra.
Insect Repellent Test
The compound prepared according to Example 1
was tested for insect repellency by the following pro-
cedures:
Mosquito Repellent Evaluation: A paper cup f~lled with
pupae of the mosquito Culex pipiens quinquefasciatus ~Say)
W8S placed in a screen cage and the pupae allowed to emerge
into adults. Sugar cubes were then saturated with 0.8
milliliters of acetone containing the test compound and, for
a control, with the same amount of acetone alone Concen-
trations o~ the test compound were utilized beginning at
1% and proceeding to lower concentrations. After the
cubes dried, they were put into the screen cage~ Repellency
was determined by the number o~ mosquito adults lighting
and feeding on the sugar cubes, with observations being
made daily. New adult mosquitos were periodically added to
the cages until all sugar cubes became non-repellent.
The number of days of complete repellency of mosquitos
from the sugar cubes were recorded. Comparative tests
were similarly conducted using the compound N,N-diethyl-
m-toluamide, commercially manufactured and employed as an
insect repellent, and generally known by the generic name
"deet". The results of the ~ests of deet and the compound
of Example 1 are shown in the follcwing Table I, the num-
bers of each colul~n represen.ing the number o~ days of
complete repellency observed using the speclfied concentra-
tion.
-4-
Table I
~ CONCENTRATION~ %
1 0.5 G.3 0.1 0 (acetone only~
Example 1 ,-æ~ ~~7 2~ 5 0
deet 11-13 6.7 5 5 0
Thus, at a concentration as low as 0.1%, the
new compound was as effective as deet in repelling mos-
quitos. At higher concentrations, it was more effective
than deet. At a concentration of 1% of the new com~ und
in the solution, after 60 days the mosquitos were still
repelled from the sugar cube and the tests were t~rminated.
Houseflies: The insect utilized for this test was housefly,
Musca domestica (L.) One hundred (100) houseflies of
mixed sexes were placed in test cages. Each test cage
consisted of a 16 ounce cupg covered with tulle netting,
and having two 3/4 ounce cups s~apled on opposite sides of
the upper, interior perimeter. One of the small cups con-
tained a sugar cube saturated with 0.8 milliliters of
acetone containing a specific concentration of the test
compound. The cube was dried and weighed before being
placed in the cup. The other small cup contained a water-
saturated cotton plug. The test cages were placed on a
turntable and rotated at 1.5 revolutions per minute to
keep the flies randomly distributed inside the cages.
After 72 hours the flies in each cage were anesthetized
with carbon dioxîde. The sugar cubes were removed and re-
weighed and the percentage weight loss (due to consumption
by the flies) recorded. The cubes with the least weight
loss are considered to show the greatest repellency. Test
concentrations of the compound ranged from 1% down to
0.1%. The weight losses of the sug~r in percent, is
shown in the following Table II.
-5-
Table II
CONCENTRATION, %
1 0 r 5 0.3 0 1 0 (Acetone onl )
Example 1 4~ 5.91 ~3 ~ 12.7 Y
deet 7.09 7.12 9.69 11.0 12.7
The novel compounds of this invention may be
used as insect repellents i~ di}uted or undiluted form.
When used in a diluted form, the compounds may be embodied
into compositions containing a relatively high or relatively
low concentration of the active compound. For example,
the active compound can be incorpora~ed into relatively
high concentration compositions such as wet sprays or
solutions in alcohol or other suitable solvents. Such
compositions may contain, in addition to the active compound,
adjuvants such as emulsifying agents, surface active agents,
antioxidants, and propellants, which may be found normally
in insect repellant preparations. The active compounds
of this invention may be employed as the sole active com-
ponent of such compositions or can be used in admixture with
other compounds having sLmilar or dif~erent utility. For
example, the novel compounds may be incorporated into
creams, lotions, powders, suntan oils, insecticides and
other preparations, which may contain pesticidal or other
useful substances, as well as to compositions of various
~ypes used for treating fabrics or articles of clothing
to render them insect repellent. In general~ compositions
for repellent use may contain from 0.5 to as high as 80
weight %, preferably from 2 to about 40 weight %, or the
novel compound.
SUPPLEMENTARY DISCLOSURE
In accordance with the teachings of the Principal
Disclosure there is provided insect repellent compounds of the
formula
¢~ (CH2 ) n~~C~R
wherein in the preferred embodiment
R is 2-methyl-1-propenyl
n is 3, and the ester moiety is substituted at the 3-
position on the pyridine ring.
With the teachings now presented in the Supplementary
Disclosure there is provided insect repellent compounds of
the formula
o
~ ( 2)n C R
wherein R is C3-C5 alkyl or C3-C5 alkenyl and n is an integer
from 1 to 3.
These compGunds may readily be prepared as outlined
in the Principal Disclosure by the reaction of an appropriate
pyridyl alkanol with an acyl chloride under the conditions
previously discussed.
m e following compounds were prepared:
TABLE III
(Invention)
~ ~H2~30CR
Compound Ring
No. _ Position R
1 3- -CH--C(CH3)2
2 2- -CH=C(CH3)2
3 4~ -CH=C(CH3)2
4 3- -CH2-CH(CH3)2
-SD 6-
57~; ~
Compound Ring
No. Position R
3- -CH=CHCH3
6 3- -CH2CH2CH3
7 3_ -CH(CH3)CH2CH3
8 4- -CH(CH3)CH2CH3
9 2- -CH(CH3)CH2CH3
4- -CH2CH(CH3)2
11 2- -CH2CH~CH3)2
12 2- -CH2CH2CH3
13 2- -C(CH3)3
14 3- -C(CH3)3
4- -C(CH3)3
16 2- -C(CH3~=CHCH3
17 3- -C(cH3)=cHcH3
18 4- -C(CH3)=CHCH3
19 3- ( 3) 2
3- -CH(CH3)2
The novel compounds of the present invention may be
used as insect repellents in diluted or undiluted form. The
following were conducted employing the compounds.
Mosquito Repellency Test
A paper cup filled with pupae of the mosquito Culex
pipiens quinquefasciatus (Say) was placed in a screened cage
and the pupae allowed to emerge into adults. Sugar cubes were
then saturated with 1~0 milliliters (ml.) of an acetone
solution containing 0.1 weight ~ of a test compound, and for
a control, with the same amount of acetone alone. After the
cubes dried, they were put into the screened cage. R~pellency
was determined by the number of mosquito adults lighting and
feeding on the sugar cubes, with observations being made daily
for fi~e days after treatment. The num~er of days of complete
-SD 7-
6 ~
repellency of mosquitos from the sugar cubes was recorded.
Housefly Repellency Test:
One hundred (100) houseflies of the species Musca
domestica (L.) of mixed sexes were placed in test cages. In
each cage was placed a sugar cube saturated with 1.0 ml. of
acetone containing 1 weight % of the test compound. The cubes
were dried and weighed before being placed in the cages. Each
cage also contained a water-saturated cotton plug to provide
moisture. The cages were placed on a turntable and rotated at
1.5 revolutions per minute to keep the flies randomly distri-
buted inside the cages. After 48 hours, the flies in each
were anesthetized with carbon dioxide. The sugar cubes were
removed and reweighed and the percentage weight loss (due to
consumption by the flies) was recorded. A repellency ratio,
calculated as the ~ weight loss of the treated sugar cube
divided by the percent weight loss of controlled sugar cube
treated with acetone only, was calculated. The lower the
repellency ratio, the greater the repellency of the test
compound.
The following table IV provides the results of the
test of the compounds previously listed for repellency for
mosquitos (Mos) and houseflies (HF). In many cases the
housefly data represents an average of several replications.
TABLE IV
HF
CompoundMos., days repellency
No. repelled ratio
1 >5 0.48
2 >5 0.38
3 >5 0.43
4 >5 0.49
3 0.73
6 3 0.69
7 >5 0.42
- -SD 8-
i'57~ ~
Compound Mos., days HF
No. repelled repellency
_ ratio
8 4 0.54
9 1 0.71
3 0.44
11 1 0.44
12 1 0.70
13 1 0.53
14 2 0.36
2-3 0.11
16 >5 0.40
17 >5 0.47
18 >5 0.54
19 4 0.47
3 0.47
~ -SD 9-
; ~ ~
